bluuebunny/crossref_metadata_2025 huggingface dataset:
A propensity score–matched comparison of fruquintinib (FRU) versus FRU combined with PD-1 inhibitors for microsatellite stability (MSS) metastatic colorectal cancer: Real-world data.
Authors: He Lina , Cheng Xiaojiao , Cheng Xin , Zhou Cong , Li Qingli , Tu Shuiping
Published: June 2024

e15564

Background: FRU has been approved for previously treated metastatic colorectal cancer (mCRC) in China and the United States, moreover it has shown synergistic effects in combination with immunotherapy in MSS CRC through immunomodulation of the tumor microenvironment. However, comparing the efficacy of FRU monotherapy (FM) and FRU combined with PD-1 inhibitors (FP) directly was rarely reported due to baseline differences in patient characteristics. To address this, we utilized the propensity score matching (PSM) to enhance the accuracy of efficacy prediction by matching relevant baseline features between the two groups. Methods: Our real-world observational study retrospectively included MSS CRC patients who have received 3rd line and above treatments from June 2019 to July 2022, and patients diagnosed with mCRC were eligible, and all patients received at least 2 cycles of FM or FP. As a result, 16 patients in the FM group and 51 patients in the FP group were enrolled. Utilizing stable LASSO (Least Absolute Shrinkage and Selection Operator) regression, we identified key clinical features relevant to outcomes for PSM. These included liver metastasis, lung metastasis, and prior chemotherapy with VEGF inhibitors. Based on these selected features, we conducted a 1:2 nearest neighbor matching algorithm to align the patients from the two groups more accurately for comparative analysis and subsequent survival analysis. The primary endpoint was progression-free survival (PFS). Results: The PSM process resulted in a matched cohort comprising 16 patients from the FM group and 32 patients from the FP group, totaling 48 patients in the analysis. The baseline characteristics of the included population were shown in Table 1. With a median follow-up of 22.87 months (95% CI: 17.00-26.07months), the median PFS in the FP group (13.27 months, 95% CI: 9.97-15.03 months) exhibited a noticeable extension compared to the FM group (4.30 months, 95% CI: 2.83-13.60 months). Additionally, the median overall survival (OS) in the FM group was 16.93 months (95% CI: 11.70-NA), and in the FP group, it was 21.30 months (95% CI: 13.67-NA). Conclusions: The FP group showed a significant increase in PFS compared to FM and PSM increased the comparability of real-world efficacy in MSS mCRC patients receiving FRU and FRU combined with PD-1 inhibitors. Further increasing the sample size may yield more valuable results. [Table: see text]
Real-world impact of KRAS mutations on clinical outcomes in metastatic colorectal cancer treated with trifluridine-tipiracil in the USA.
Authors: Labadie Brian William , Birch Cierra , Quayle Carol , Lou Emil , Algaze Sandra , Xiu Joanne , Park Soo J
Published: June 2024

e15566

Background: Defining the impact of KRAS mutation status on outcomes to standard of care treatments in metastatic colorectal cancer (mCRC) is of increasing clinical relevance. We interrogated a large real-world genomic database to further explore the association between KRAS mutations and benefit to trifluridine-tipiracil (FTD-TPI) in patients with mCRC. Methods: 19,364 patients with mCRC and known KRAS mutation status were analyzed by next-generation sequencing (NextSeq, 592 Genes; NovaSeq, whole exome sequencing (WES)) at Caris Life Sciences. Real-world overall survival (rwOS) and time on treatment (ToT) was inferred from insurance claims data and calculated from time of start of treatment with FTD-TPI to last contact and time from first to last treatment with FTD-TPI with comparison done by the Kaplan-Meier test, respectively. Chi-square test was applied where appropriate, with p-value adjusted for multiple comparisons (p < 0.05). Results: 764 of 10,571 (7.2%) patients with wild-type (WT) KRAS, 768 of 6,984 (11%) with KRAS G12 mutation, and 170 of 1,809 (9.4%) with KRAS G13 mutation received FTD-TPI. Age distribution was similar among groups. Sidedness of primary site was reported in 692 (40.3%) patients; an increased proportion of right-sided tumors was observed in KRAS G12 (53.4% vs. 28.3%, p < 0.0001) and G13 (56% vs 28.3%, p < 0.0001) groups compared to KRAS WT. An increased proportion of TP53 mutations in KRAS WT was observed compared to KRAS G12 mutation (87% vs. 70%, p < 0.0001) and KRAS G13 mutation groups (87% vs. 75%, p < 0.0001). KRAS G12 mutation was associated with shorter median rwOS compared to KRAS WT (7.33 vs. 8.43 months (mo), HR 1.13 (95% CI 1.11-1.42), p = 0.041). KRAS G13 mutation was associated with similar rwOS to KRAS WT. Median ToT was shorter in patients with KRAS G12 mutations than KRAS WT (1.8 vs. 2 mo, HR of 1.22 (95% CI 1.11-1.42), p < 0.001). Median ToT was longer in patients with KRAS G13 versus KRAS G12 (2.3 vs. 1.8 mo, HR 0.82 (95% CI 0.68-0.98), p = 0.032). Conclusions: To our knowledge, this is the largest primarily US-based cohort of mCRC treated with FTD-TPI to be reported. KRAS G12 mutation, but not KRAS G13 mutation, was associated with shorter rwOS and ToT compared to KRAS WT, despite enrichment of TP53 and BRAF mutations in the KRAS WT group. This finding is consistent with previously published analyses of large randomized prospective trials of FTD-TPI in mCRC and further support KRAS mutation status as a predictive biomarker in this setting. [Table: see text]
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]
Factors influencing the mortality risk of heart failure in patients receiving antineoplastic immunotherapy: A national inpatient database study 2016-2020.
Authors: Shah Purva , Orakzai Abdullah Ahmad , Kharel Himal , Sanjeevi Aditya , Eltaher Basant , Easow Jose M.
Published: June 2024

e24011

Background: Immunotherapy is increasingly being used for management of solid and lymphoproliferative tumors due to their more desirable side effect profile as compared to traditional cancer therapies. However, these medications are associated with cardiac complications and little is known about the factors influencing the prognosis in these patients. Methods: This is a retrospective analysis of the National Inpatient Database from 2016 to 2020 using the International Classification of Diseases (ICD) 10 codes performed with STATA BE 18.0. Chi square test was used for crude analysis and multivariate logistic regression was performed to assess the risk of inpatient death among cancer patients with heart failure receiving immunotherapy. Results were adjusted for potential confounders like age, gender, race, hypertension, diabetes, coronary artery disease, smoking, and alcohol consumption. Multicollinearity of the model was assessed using Variance Inflation Factor (VIF) post-estimation test. Results: Out of 5166 cancer patients receiving immunotherapy with a mean age of 43.63 土 26.33 years and 41% females, 45 patients had heart failure. Logistic regression showed that heart failure was significantly associated with mortality (LR 𝜒² 38.74, p value < 0.001) on adjusting for potential confounders. Although the effect size was small, increased age (OR 1.025, CI 1.01-1.04) had a significantly higher risk of mortality. Patients belonging to the female gender and white, hispanic, and asian races had a lower risk of mortality while those belonging to the african american race and those with coronary artery disease had a higher mortality risk, although not statistically significant. Diabetes and alcohol consumption had a fourfold and sixfold increased risk of mortality respectively. Hypertension and smoking that are known to increase mortality risk in heart failure patients showed a paradoxically protective effect in this cohort. Conclusions: This study highlights the importance of risk stratification and prognostication among patients with heart failure receiving antineoplastic immunotherapy. Increased age, african american race, diabetes, alcohol consumption, and coronary artery disease have shown an increased mortality risk in these patients. [Table: see text]
Effect of sodium-glucose cotransporter 2 inhibitor dapagliflozin on systemic H-FABP and monocyte-to-lymphocyte ratio in preclinical models of antracycline induced cardiotoxicity.
Authors: Maurea Nicola , Canale Maria Laura , Bisceglia Irma , De Laurentiis Michelino , Bruzzese Francesca , Palma Giuseppe , Luciano Antonio , Iovine Martina , Paccone Andrea , Giacobbe Ilaria , Giordano Vienna , Izzo Francesca , Barbato Matteo , Arianna Raffaele , Inno Alessandro , Quagliariello Vincenzo
Published: June 2024

e24012

Background: Anthracyclines are an effective and widely used chemotherapy agent in the treatment of multiple solid organ tumors and hematologic malignancies. The use of anthracyclines as a standard cancer therapy is limited by the potential for the development of cardiac dysfunction, arrhythmias, and clinical heart failure. Dapagliflozin exerts several cardiometabolic benefits in patients with and wthout T2DM through SGLT2-NLRP3 mediated pathways. In this study, we highlighted on new beneficial properties of Dapagliflozin in preclinical models of doxorubicin-induced cardiotoxicity. Methods: Female C57Bl/6 mice were untreated (Sham, n = 6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n = 6), DAPA at 12 mg/kg (DAPA, n = 6) or doxorubicin combined to DAPA (DOXO–DAPA, n = 6). After treatments, plasma levels of H-FABP and monocyte-to-lymphocyte ratio were determined through selective quantitative methods. Results: Dapagliflozin associated to Doxorubicin reduces of 48,7% plasma levels of H-FABP compared to DOXO group (p < 0.001). Myocardial expression of H-FABP were also reduced, indicating cardioprotective properties of SGLT2i. Moreover, monocyte-to-lymphocyte ratio was strongly enhanced after DOXO therapy, indicating systemic pro-inflammatory properties; notably, Dapagliflozin reduced of 32,8% the monocyte-to-lymphocyte ratio compared to only DOXO treated mice (p < 0.005). Conclusions: For the first time, Dapagliflozin demonstrated a significant reductions of monocyte-to-lymphocyte ratio during doxorubicin therapy, indicating new potential pathways of cardioprotection in cancer patients
Effect of sodium-glucose cotransporter 2 inhibitor dapagliflozin on ejection fraction reduction, myocardial and renal NF-κB expression and systemic pro-inflammatory biomarkers in models of short-term doxorubicin cardiotoxicity.
Authors: Quagliariello Vincenzo , Canale Maria Laura , Bisceglia Irma , Inno Alessandro , Bruzzese Francesca , Palma Giuseppe , Luciano Antonio , Iovine Martina , Giacobbe Ilaria , Maurea Fabrizio , Giordano Vienna , Izzo Francesca , Barbato Matteo , Arianna Raffaele , Berretta Massimiliano , Maurea Nicola
Published: June 2024

e24013

Background: Anthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in cancer patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exerts multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease and heart failure with reduced and preserved ejection fraction. We hypothesized that the SGLT2i Dapagliflozin administered before and during doxorubicin therapy, could improve cardiac function and reduce pro-inflammatory pathways in preclinical models. Methods: Female C57Bl/6 mice were treated for 10 days with a saline solution or DOXO (2.17 mg/kg), DAPA (10 mg/kg) or DOXO combined to DAPA. Systemic levels of ferroptosis-related biomarkers, galectin-3, hs-CRP and pro-inflammatory chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. After treatments, immunohistochemical staining of myocardial and renal p65/NF-kB was performed. Results: DAPA prevented the reduction of radial and longitudinal strain and ejection fraction after 10 days of treatment with DOXO. A reduced myocardial expression of NLRP-3 and MyD-88 was seen in DOXO-DAPA group compared to DOXO mice. Systemic levels of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with DAPA. Serum levels of galectine-3 and hs-CRP were strongly enhanced in DOXO group; contrary, their expression were reduced in DAPA-DOXO group. Troponin-T, BNP and NT-pro-BNP were strongly reduced in DOXO-DAPA group, revealing cardioprotective properties of SGLT2-i. Mice treated with DOXO and DAPA exhibited reduced myocardial and renal NF-kB expression. Conclusions: The overall picture of the study encourages the use of DAPA in primary prevention of cardiomyopathies induced by anthracyclines in cancer patients.
Impact of cardiac arrhythmias on in-hospital mortality in patients with cytokine release syndrome: Insights from National Inpatient Sample.
Authors: Karam Wissam , Akkawi Abdul Rahman , Zakhour Joud , Alqam Anas , Shah Raj N. , Nabbout Nassim H.
Published: June 2024

e24017

Background: Cytokine release syndrome (CSR) is a pervasive inflammatory response characterized by elevated body temperature and multi-organ dysfunction. This syndrome is linked to chimeric antigen receptor (CAR)-T cell therapy, various immunotherapies, or haploidentical hematopoietic cell transplantation (HCT). It can manifest as a fever, fatigue, headache, rash, diarrhea, arthralgia, and myalgia. In some cases, it can progress to hypotension, hypoxia, and an uncontrolled systemic inflammatory response leading to circulatory collapse, pulmonary edema, renal damage, and multi-organ failure. Cardiac evaluation in the context of CSR is crucial for assessing these manifestations, but little is known about the arrhythmias associated with this therapy, and there is limited information in the literature. Methods: A retrospective study using the National Inpatient Sample to identify patients diagnosed with CRS, and the arrhythmias they experienced during their hospitalizations between January and December 2020. The primary endpoint was the incidence of various arrhythmias. Furthermore, Independent predictors of in-hospital mortality were analyzed, with p values, adjusted odds ratios (aOR) and confidence intervals (CI) calculated for each variable. Results: A total of 4675 patients were diagnosed with CRS in 2020, 39% of whom were females. The mortality rate of patients with CRS was 22%. In addition, the mortality rate of patients who developed arrhythmias was 43% while that of patients who did not was 17% (p < 0.01). The mean age was higher in the arrhythmia cohort compared with the non-arrhythmia cohort (70 vs 60.7 years, p < 0.01). Predictive factors associated with increased mortality included development of arrhythmias, age, hispanic race, asian or pacific islander race, obesity, previous myocardial infarction, and electrolyte abnormalities with an aOR of 2.22 (P < 0.01, CI 1.51-3.28), 1.03 (P < 0.01, CI 1.01-1.05), 1.85 (P = 0.04, CI 1.02-3.34), 2.57 (P = 0.014, CI 1.02-3.34), 1.72 (P = 0.018, CI 1.09-2.69), 3.26 (P = 0.008, CI 1.36-7.8), and 4.19 (P < 0.01, CI 2.7-6.4) respectively. Female sex was found to be protective against mortality with an aOR of 0.5 (P = 0.004, CI 0.31-0.8). Conclusions: Our study reveals that developing arrhythmias is more common in older patients with CRS. Patients diagnosed with arrhythmias during their hospitalization experienced poorer outcomes. Adjusted predictors of mortality include the development of arrhythmias during hospitalization, age, hispanic race, asian or pacific islander race, obesity, previous myocardial infarction, and electrolyte imbalances. Additionally, female sex was found to be a protective against mortality. Given these findings, physicians should strive to be more vigilant when treating patients with CRS who have any of these predictors of mortality until further data is available.
Cardio-Oncology Awareness: A multidisciplinary survey amongst health care trainees and practicing professionals at academic institutions.
Authors: Bansal Shruti , Misra Shagun , Khanna Rupali , Lal Punita , Sarangi Satya Sadhan , Kapoor Aditya , Kumar Shaleen
Published: June 2024

e24023

Background: The awareness of cancer therapy-related adverse cardiac effects is incited by recent literature on cardiotoxicity incidence and detection strategies. Despite availability of guidelines, cardiotoxicity monitoring and treatment are not structurally performed across institutions. Aim: Assessing knowledge of health care professionals’ cardiac complications of cancer treatments, current perspectives on cardio-oncology ultimately to determine an agenda for improvements in practice. Methods: A web-based survey (Google Forms) was adapted from that of Ottawa Hospital Research Institute’s survey, consisting of 45 questions organized into 7 sections, modified according to our local needs and circulated to cardiologists, oncologists (radiation, medical) practicing or training in a multi-disciplinary setup and academic centers. Fortnightly reminders were sent for to receive a maximum response. The survey enquired about implementing respondent’s perception of cardio-oncology, availability of cardio-oncology services at the respondent’s institution, opinions towards current practice. A descriptive statistical analysis was carried out. Results: Fifty-five professionals completed the survey, of which 12 were cardiologists, 31 radiation oncologists, and 12 medical oncologists. Majority, 31 (54.5%) were trainees and only 1.8% had some formal training in cardio-oncology while 20% respondents reported to have a formal cardio-oncology training programme. Nearly 90% understood cardio-oncology as a stream to be able to identify side-effects and refer for treatment to the cardiologists while 84% felt that timely referral would improve outcomes.72% recognized follow-up and 67.3% felt patient education to be important component. Awareness of cardio-oncology guidelines was reported by 38.2% respondents. In the setting of metastatic cancer, there was a difference in risk tolerance for cardiotoxicity with the majority accepting 1-5% risk in curative setting and 56% accepting > 5% risk of cardiotoxicity in the metastatic setting. None of the institutions reported on having a formal training programme. Limited infrastructure (54.5%) and limited interest (47.3%) were cited the most common reasons. Conclusions: This survey identified that professionals recognize cardio-oncology services to be an important component of cancer treatment. Lack of formal training and awareness about guidelines was reported. There is a felt need for collaboration between cardiologists and oncologists to improve cardiovascular outcomes of cancer patients.
Predictors of long-term survival in immune checkpoint inhibitor (ICI)-associated myocarditis.
Authors: Wu Chia-Yun , Dubey Nikhil , Zubiri Leyre , Rouhani Sherin Juliet , Sun Joie , Neilan Tomas G. , Reynolds Kerry Lynn , Zlotoff Daniel A.
Published: June 2024

e24026

Background: ICI-associated myocarditis carries a high morbidity and mortality, with close to half of patients experiencing major adverse cardiac events (MACE). Risk factors previously associated with short-term MACE include troponin T (TnT), neutrophil/lymphocyte ratio (NLR), and absolute lymphocyte count (ALC). In this study, we aimed to analyze the predictors of long-term survival. Methods: This single-center retrospective study included 37 patients diagnosed with ICI-associated myocarditis at Massachusetts General Hospital between March 2016 and March 2022. We collected demographics, diagnostic results, and myocarditis treatments from the electronic medical record. Patients were grouped by survival time: short-term ( < 30 day), intermediate (30 to 360 day), or long-term ( > 360 days) survival. We used chi-square and Kruskal-Wallis tests for descriptive statistics. Cut-off points of continuous variables were determined by ROC curve. Predictors of survival were analyzed by logistic regression models. Results: The cohort consisted of 29 males and 8 females with a median age of 75 years (IQR 68-79), and median follow-up of 5.6 months (IQR 0.5-14.9). The median time from ICI start to myocarditis onset was 50 days (IQR 36-91). Ten, 14, and 13 patients were in the short-term, intermediate, and long-term survival groups, respectively. By univariate analysis, predictors of long-term survival included initial NT-proBNP ≤ 450, NLR ≤ 4.44, ALC ≥ 1122, normal EKG QTc interval (≤ 450 ms in male or ≤ 460 ms in female), and TnT decrement ≥ 42% by day 8 of immunosuppression (Table 1). All patients with long-term survival presented with a normal left ventricular ejection fraction (LVEF ≥ 55%), which made it uninterpretable using logistic regression models. Normal LVEF was significantly associated with long-term survival by using chi-square test (p = 0.002). While TnT elevation > 75x the upper limit of normal (ULN) was strongly associated with short-term survival (p = 0.001), it was not associated with long-term survival (p = 0.23). The use of second-line immunosuppression in addition to corticosteroids did not have a significant impact on long-term survival (p = 0.69). Conclusions: NLR, ALC, NT-proBNP, QTc interval, and a substantial decrease in TnT at day 8 after immunosuppression are all associated with long-term survival in ICI myocarditis. [Table: see text]
Pancreatic-enzyme replacement therapy with pancrelipase plus chemotherapy for patients with pancreatic adenocarcinoma with cachexia and exocrine pancreatic insufficiency (PANCAX-3).
Authors: Ebia Matthew , Kabir Shaowli , Minton Brian , Abbas Anser Ali , Osipov Arsen , Gong Jun , Hendifar Andrew Eugene
Published: June 2024

e24059

Background: Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency (EPI). The utility of this therapy for patients with EPI in the setting of pancreatic ductal adenocarcinoma (PDAC) is unclear. We report results of a single site phase 2 trial for PERT with Pancreaze® plus standard of care (SOC) chemotherapy in PDAC patients with cachexia and EPI. The primary outcome measure was to assess feasibility of completing PERT during the first 8 weeks of treatment. Secondary outcome measures included weight stability, mean change in stool frequency, stool consistency from Cycle 1 (C1) to Cycle 3 (C3) (after 8 weeks of PERT), mean change in serum levels of fat soluble vitamins (A, D, E, K) from baseline to end of study, functional activity, and safety. Methods: Feasibility was defined as adherence to therapy of ≥50% of the needed total lipase units in the first 8 weeks of treatment (84,000 IU lipase units per meal, 42,000 IU lipase units per snack). Data are presented as frequencies (%) for categorical variables and means ± standard deviation for continuous variables. Weight stability, stool frequency, fat soluble vitamin levels, walk speed, and hand grip strength compared using two-sample paired t-tests. Stool consistency (Bristol stool type) compared using Fisher’s exact test. Results: Of 36 patients enrolled, 30 were evaluable for primary endpoint. Median age was 70. 73.3% (22/30) were female. 33.3% (10/30) were borderline resectable, 33.3% (10/30) locally advanced, and 33.3% (10/30) advanced/metastatic. 30 patients completed 8 weeks of PERT and 96.7% (29/30) were compliant. Efficacy results include PR (6.7%, 2/30), SD (66.7%, 20/30) and PD (23.3%, 7/30). Imaging not available for 1 patient. 6 patients experienced grade 1/2 GI toxicities (nausea, bloating, diarrhea, abdominal pain) deemed possibly/probably related to PERT. Grade 3/4 AEs included fatigue, infection, and hematologic toxicities deemed unrelated to PERT. Among evaluable patients, weight remained stable (-0.01±0.07 kg/BMI, p = 0.511) and there was a trend toward reduced stool frequency (p = 0.052) from C1 to C3. Stool consistency from C1 to C3 showed significant association (p = 0.035). Serum fat soluble vitamins, functional activity by walk speed and hand grip strength were also explored and no statistically significant differences were observed from C1 to C3 among the evaluable patients. Conclusions: PERT plus SOC chemotherapy for PDAC patients with cachexia and EPI is feasible and well-tolerated. Patients taking PERT experienced weight stability. PERT may aid in reducing stool frequency and further analysis is warranted into how PERT affects stool consistency. Clinical trial information: NCT04098237 .
Patterns of referral to supportive oncology (SO) practice embedded in a cancer center and impact of timing of referrals on end-of-life outcomes.
Authors: Crowley Fionnuala , Zeng Li , Sheng Tianxiang , Bilani Nadeem , Hobensack Mollie , Popp Beth , Afezolli Debora , Kelly Lauren , Wey Winston , Chen Joanna , Austin Vanessa , Bajwa Aleena , Easton Eve , Pagala Arlyn , Kim Emily , Smith Cardinale B. , Gelfman Laura P.
Published: June 2024

e24064

Background: ASCO guidelines recommend early palliative care (PC) for patients with advanced cancer, defined as within eight weeks of diagnosis, to enhance survival and quality of life. It is unclear which subsets of patients are referred “late” to PC and how timing of referral impacts cancer outcomes and end-of-life care. Methods: Patients >18 years with first SO consult between 01/01/2021-06/30/2023 were included. Data on patient demographics, acute healthcare and hospice utilization, cancer treatment and mortality was extracted from the electronic medical record (EMR) and claims database. Early referral to SO was defined as visit < 3 months after diagnosis of advanced disease, delayed referrals > 3 months and late consults as < 30 days from death. We used descriptive statistics to describe patients’ sociodemographics, clinical characteristics and healthcare utilization. Multinomial logistic regression analysis was utilized to evaluate how patient characteristics influenced the timing of referrals. To examine the effects of late referral on inpatient (IP) and intensive care unit (ICU) stay durations, we applied a hurdle model. Results: Total sample included 1229 patients; majority had ECOG < 2 and received one line of treatment at time of consult, 87% had solid tumors, of whom 74% had stage 4 disease. The solid tumors most referred were gastrointestinal cancers (25%), lung cancer (14%) and head and neck cancers (13%). Early referral rates across cancer groups differed significantly 53% Head and Neck, 48% GI, 46% Lung, 43% GYN, 29% GU, 11% Breast, and 31% Other (p < 0.001). The most common reason for referral was physical symptom management (98%). The median ESAS symptom burden was 5 (range 0-10) symptoms. At time of analysis, 431 (35.1%) patients had died of which 256 (59%) were in-hospital deaths. Of the deceased patients, late referral ( < 30 days from death) showed a trend, although not statistically significant, toward higher in-hospital mortality rates, (Odds Ratio: 1.13; 95% CI: 0.57-2.24), and a trend toward reduced likelihood of hospice enrollment(Odds Ratio: 0.73; 95% CI: 0.36-1.49). Notably, late referral significantly increased the duration of IP stays (p < 0.001) and ICU stays (p = 0.004) in last 30 days of life, without change in admission to IP (p = 0.68) or ICU (p = 0.86). Conclusions: The delivery of the guideline-directed "early” consult among patients with advanced cancer is variable. Preliminary analysis showed a trend towards higher in-hospital mortality rates and lower hospice referral for patients referred < 30 days from death among “late” consults. Further subgroup analysis is ongoing. [Table: see text]