bluuebunny/crossref_metadata_2025 huggingface dataset:
KEYNOTE-158: Final analysis of pembrolizumab in patients of Chinese descent with microsatellite instability-high/mismatch repair deficient advanced solid tumors.
Authors: Xu Jianming , Mao Yimin , Xu Nong , Bai Yuxian , Wang Dong , Chen Xiaojun , Yin Xianli , Deng Yanhong , Yang Jianwei , Zhang Jieqing , Tang Jie , Huang Yi , Li Jiayi , Luo Suxia , Xu Miaomiao , Li Nan , Mao Yixiang , Gozman Alexander , Wu Xiaohua
Published: June 2024

e15137

Background: The multicohort non-randomized, phase 2 KEYNOTE-158 (NCT02628067) trial supported the FDA approval of pembrolizumab for unresectable or metastatic microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) solid tumors. Incidence of advanced MSI-H/dMMR tumors in patients (pts) of Chinese descent is similar to that in Western populations. In KEYNOTE-158 cohort L, we evaluated the antitumor activity of pembrolizumab in pts of Chinese descent with MSI-H/dMMR solid tumors. We previously reported an ORR of 70% in 20 pts from cohort L. Here we present results of the final analysis for 30 pts with 18 months (mo) of follow up. Methods: Eligible pts of Chinese descent from China aged ≥18 years were enrolled. Pts had to have confirmed unresectable or metastatic MSI-H/dMMR tumors, and ≥1 prior lines of therapy. Pts received 200 mg pembrolizumab Q3W for up to 35 cycles, until progression, unacceptable toxicity, or pt/investigator withdrawal. MSI-H/dMMR status was assessed centrally by PCR and IHC. The primary endpoint was ORR per RECIST 1.1 by central review. Secondary endpoints were DOR, PFS, OS and safety. The database cut-off date was May 5, 2023. Results: A total of 30 pts were enrolled; 7 (23%) were aged ≥65 years, and 20 (67%) were female. At data cut-off, 14 (47%) pts discontinued treatment; 12 (40%) due to progressive disease, 1 (3%) due to adverse events (AE), and 1 (3%) due to physician decision. The median follow-up (range) was 18.0 mo (6.4 – 32.7). The ORR was 66.7% (6 CR; 14 PR [95% CI: 47.2%- 82.7%]). The median DOR was not reached (NR) (range, 1.8+ - 29.5+) with a 12-mo DOR rate of 85.9%. Median PFS was NR (95% CI: 8.1-NR) with an 18-mo PFS rate of 63.0%. The median OS was NR (95% CI: 19.1, NR) with an 18-mo OS rate of 78.8%. Treatment-related AEs were reported in 22 (73%) pts. Grade 3-4 treatment-related AEs occurred in 7 (23%) pts. There were no grade 5 AEs. Immune-mediated AEs occurred in 11 pts (37%); 2 (7%) had grade 3 AEs (myositis or rash in 1 pt each). No grade 4-5 immune-mediated AEs occurred. Conclusions: Pembrolizumab continues to provide clinically meaningful antitumor activity and durable responses with a manageable safety profile in pts of Chinese descent with MSI-H/dMMR tumors. No new safety signals were identified. These results are consistent with those reported in the global population and further support the use of pembrolizumab in pts of Chinese descent with MSI-H/dMMR tumors. Clinical trial information: NCT02628067 .
EXPRESS study: A trial exploring the association of low level of genomic alteration with exceptional and unexpected response to targeted therapies in patients with advanced solid tumors.
Authors: Le Saux Olivia , Girard Elodie , Leslie Lori , Bachelot Thomas , Pierga Jean-Yves , Barlesi Fabrice , Albiges Laurence , Lebbe Celeste , Boige Valerie , Frenel Jean-Sebastien , Spaeth Dominique , Guillot Aline , Heudel Pierre Etienne , Gardner Miriam , Durando Xavier , Peron Julien , Kamal Maud , Legrand François , Lusque Amelie , Bieche Ivan ,   Centre Léon Bérard
Published: June 2024

e15140

Background: Small subsets of pts treated with targeted therapies (TT) present exceptional and unexpected response (1-10%), which could be driven and correlated by a low level of genomic alterations in genes identified as causally implicated in cancer. Conversely, the multiplication of the genomic alterations in such genes would decrease the oncogenic de-addiction process. Methods: EXPRESS is an exploratory, multicenter, prospective trial conducted in pts with locally advanced or metastatic solid tumors, who presented an exceptional and unexpected response to an antineoplastic TT. This research aimed to explore whether tumors with a low level genomic alteration (mutation, amplification, deletion) as assessed by whole exome sequencing (WES) are associated with exceptional and unexpected response. Secondary endpoints including the identification of novel candidate somatic molecular profiles and host immunologic characteristics susceptible to drive exceptional and unexpected response will be reported later. Results: 439 pts were identified over 32 centres from December 2016 to April 2021. Out of 270 pts confirmed with an exceptional response by our review committee of cases, 183 were included in the EXPRESS study. Exceptional responder population is summarised (Table). Out of 183, WES analysis was performed for 103 pts (56.3%). Genomic analysis failure was predominant in the breast and lung cohort (60.9% and 52.5%). The number of genomic alterations in the EXPRESS cohort was lower than in the TCGA control cohort (median[Q1-Q3]: 11[7-17] vs 19 [11-32], p<0.001). A lower number of genomic alterations was also reported in the melanoma (8[5-13] vs 33[17-51], p<0.001) and lung cancer cohort (8[5-17] vs 22[13-34], p<0.001) but not in the breast and kidney cohorts (13[10-21] vs 17[10-29], p=0.41 and 12[9-14] vs 11[7-17], p=0.89). Conclusions: Compared to the TCGA cohort, a low level of genomic alteration is associated with exceptional response in pts with lung cancer and melanoma. A comparison with a matched population based on genomic criteria in the TCGA is undergoing and will be presented at the conference. Clinical trial information: NCT02701907 . [Table: see text]
Overcoming chemoresistance in triple-negative breast cancer (TNBC): Targeting PD-L1 stability and ferroptosis through integrated lipid metabolism and immune modulation.
Authors: Yang Sujin , Tang Jinhai , Zhang Jian
Published: June 2024

e15149

Background: Triple-negative breast cancer (TNBC) is notorious for its aggressive nature and high recurrence rates, exacerbated by the lack of specific molecular targets, leading to poor prognosis and emergent chemoresistance. Our study explores ferroptosis mechanisms in TNBC, focusing on the interaction between lipid metabolism and immune system modulation to identify targets that enhance chemosensitivity, potentially improving chemotherapy efficacy. Methods: We employed RNA transcriptomics, proteomics, metabolomics, and lipidomics to compare gene transcription, protein expression, and metabolic profiles between TNBC cell lines MDA-MB-231/ADR (doxorubicin-resistant) and MDA-MB-231/S (sensitive). The impact of the ferroptosis inducer Erastin on MDA-MB-231/ADR was assessed through lipidomics. We also performed gene expression profiling on 152 TNBC patients unresponsive to Anthracycline-based chemotherapy, correlating with data from TCGA and METABRIC. Functional loss and gain experiments were undertaken to explicate the role of the SCD1-TRIM28-PD-L1 axis in mediating ADR resistance. Immunohistochemistry and RT-qPCR analyses were performed on tumor tissues and serum EVs from TNBC patients to identify chemosensitivity-enhancing targets. Results: Our investigation revealed marked transcriptional and proteomic variances between MDA-MB-231/ADR and MDA-MB-231/S cell lines, with SCD1 showing significant upregulation at both mRNA and protein levels. Metabolomic analyses revealed distinct lipid metabolic profiles between these two cell lines. Further studies found that Erastin treatment increased PD-L1 expression, along with changes in SCD1, p53, and TNFAIP3 expression levels. These molecules are closely associated with poor prognosis and resistance to therapy. Our findings also elucidated that TRIM28 modulates PD-L1 stability via SUMOylation and facilitates p53 ubiquitination and degradation through a TRIM28-MDM2 dependent pathway, thereby impacting immune surveillance and therapeutic response. Additionally, in TNBC patients treated with anthracycline-based chemotherapy, higher SCD1 and TNFAIP3 but lower TRIM28 expressions were observed in the PD/SD group compared to PR/CR. Similar expression patterns were observed in serum EVs. Conclusions: Our study highlights the potential of targeting the SCD1-TRIM28-PD-L1 axis in TNBC to overcome chemoresistance. We propose combining SCD1 inhibition with ferroptosis inducers to enhance PD-L1 blockade efficacy, offering a promising approach for TNBC patients with limited response to Anthracycline-based chemotherapy. This investigation represents a pivotal step towards advancing targeted therapeutics in TNBC, potentially transforming the clinical management of this aggressive and refractory breast cancer subtype.
Changes in US colorectal cancer mortality trends over the past 20 years.
Authors: Tan Jia Yi , Yeo Yong Hao , Ng Wern Lynn , Fong Zhi Ven , Brady Justin T.
Published: June 2024

e15543

Background: In the last two decades, colorectal cancer (CRC) mortality has been decreasing in the United States (US). However, the mortality trends for the different subtypes of CRC, including different sides of colon, rectosigmoid, and rectal cancer remain unclear. Methods: We analyzed death certificate data from CDC WONDER from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals of CRC and its different subtypes and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Results: From 1999 to 2020, 1,166,099 deaths were attributed to CRC, of which 957,182 deaths (82.08%) were due to colon cancer, 148,862 deaths (12.77%) from rectal cancer, and 60,055 deaths (5.15%) from rectosigmoid cancer. The overall CRC rates decreased significantly from 26.42 (95% CI, 26.20-26.64) to 15.98 (95% CI, 15.84-16.12) per 100,000 individuals, with AAPC of -2.41 (95% CI, -2.55, -2.27). However, the AAMR of rectosigmoid cancer increased significantly from 0.82 (95% CI, 0.78 -0.86) to 1.08 (95% CI, 1.04-1.11) per 100,000 individuals and the AAMR of right-sided colon cancer increased from 0.57 (95% CI, 0.54-0.60) to 0.70 (95% CI, 0.67-0.73) per 100,000 individuals, with AAPC of +1.10 (95%, 0.21-2.00) and +2.06 (95% CI, 0.85 - 3.27) respectively. Men had higher AAMR of CRC than women (23.90 [95% CI, 23.84-23.96] vs. 17.03 [95% CI, 16.99-17.08] per 100,000 individuals). African Americans had the highest AAMR of CRC (26.93 [95% CI, 26.79-27.07]), followed by Whites (19.60 [95%, 19.56-19.64] per 100,000 individuals), American Indians (14.53 [95%, 14.15-14.92] per 100,000 individuals), and Asians (13.04 [95%, 12.89-13.19] per 100,000 individuals). The overall AAMR of CRC decreased for those aged ≥ 50 years but increased significantly from 1.02 to 1.58 per 100,000 individuals for those aged 15-49 years, with an AAPC of +0.75. The AAMR from CRC was the highest in the Midwest (21.04 [95% CI, 20.96-21.12] per 100,000 individuals), followed by the South (20.51 [95% CI, 20.44-20.57]), the Northeast (20.30 [95% CI, 20.22-20.38] per 100,000 individuals), and the West (18.03 [95% CI, 17.95-18.10] per 100,000 individuals). Rural populations had higher AAMR than urban populations (22.40 [95% CI, 22.30-22.49] vs. 19.60 [95%, 19.56-19.64] per 100,000 individuals). Conclusions: Although overall CRC mortality declined, there were rising trends in young-onset CRC, rectosigmoid cancer, and right-sided colon cancer. Disparities persist in terms of sex, race, geographic region, and urbanization level, emphasizing the need for targeted public health measures.
Prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data.
Authors: Jafri Mohsin Saleet , Amniouel Soukaina
Published: June 2024

e15548

Background: FOLFOX and FOLFIRI chemotherapy are considered standard first-line treatment options for colorectal cancer (CRC). However, the criteria for selecting the appropriate treatments have not been thoroughly analyzed. Here, we aim to use machine learning and genetic profiles to identify precise multi-gene panels that can predict the response to 5-Fluorouracil-based chemotherapy in colorectal cancer patients. Methods: The genetic profiling data, including drug response profiles, were retrieved from the Gene Expression Omnibus (GEO) database. These datasets were used to train and validate machine learning models. Feature selection methods, such as least absolute shrinkage and selection operator (LASSO) and variable selection from random forests (varSelRF) and various algorithms, such as Random Forest and Support Vector Machines, were applied to develop predictive models. Functional enrichment and network analyses were performed using Ingenuity Pathway Analysis (IPA). Results: This study identified relevant gene signatures at two stages of colorectal cancer: primary and metastasis using two different chemotherapy regimens, FOLFOX and FOLFIRI. The predictive models achieved an average prediction accuracy of 93% in identifying drug response outcomes across multiple chemotherapy regimens. The application of the machine learning model suggested that 28.6% of patients who failed the treatment therapy they received would benefit from the alternative treatment. Conclusions: The developed machine learning models demonstrate potential for guiding clinicians in selecting the most effective treatment options based on individual genetic profiles. With additional clinical validation, this approach could lead to improvements in treatment outcomes for patients with CRC and other cancers.
PIPAC in patients with peritoneal metastases from gastrointestinal tract (PIPOX): An open label, non-comparative phase 1/2 dose escalation and expansion trial.
Authors: Dumont Frederic , Kepenekian Vahan , Passot Christophe , Ezanno-Manasterki Anne-Cecile , Pocard Marc , Raoul Jean-Luc , Lelievre Benedicte , Hiret Sandrine , Senellart Hélène , Pein Francois J. L. , Raimbourg Judith , Thibaudeau Emilie , Paul Julie , Glehen Olivier
Published: June 2024

e15561

Background: Withmodern systemic chemotherapy, survival remain poor for patient withadvanced isolated peritoneal metastases from gastrointestinal tract. We aimed to assess the safety and efficacy of PIPAC to oxaliplatin in combination or not with systemic chemotherapy. Methods: We did a phase 1/2, open label, non-comparative, dose escalation and expansion trial of PIPAC to oxaliplatin forpatients with peritoneal cancer index (PCI) more than 5, 13 and 15 for respectively a gastric, small bowell and colorectal cancer primary; who had received at least three months of systemic chemotherapy. PIPAC cycle lengths was 4 to 6 weeks with systemic chemotherapy allowed 15 days after each PIPAC. PCI and oxaliplatin concentration tumor was assessed every PIPAC cycles. Main endpoints were, tolerability, tumor response and survival. Results: Between2017 to 2020, 34 for patients were enrolled in three centers, in this phase 1/2 study of whom 25 were evaluable at recommanded dose of phase I of 90 mg/m2 plus systemic 5-FU. At this dose, safety profile showed acceptable tolerability. 8 patients (32%) had grade 3/4 treatment related adverse event. Minors (grade 1/2) adverse events were mainly abdominal pain (n = 19, 76%) and nausea (n = 16, 64%). Before inclusion patients received a median of 2 [1-4] chemotherapy lines and had a median PCI of 22.5 [7-29]. Median PFS was 6.1 months and median OS was 13 months. Conclusions: In patients with advanced and refractory peritoneal metastasis, PFS of 6.1 months is encouraging. A prospective randomized phase II study is required. Clinical trial information: NCT03294252 .
Stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer: Updated findings from a single-arm, prospective phase II trial (RIFLE).
Authors: Chen Yajie , Wang Kun , Zhiyuan Zhang , Zhang Hui , Yang Wang , Wu Ruiyan , Zhou Menglong , Zhang Zhen , Xia Fan
Published: June 2024

e15570

Background: Stereotactic ablative radiotherapy (SABR) has been shown to sensitize immunotherapy through inducing immunogenic death and remodeling the tumor immune microenvironment. In addition, anti-angiogenic therapy exhibits synergistic antitumor effects with PD-1/PD-L1 antibodies through its immunomodulatory effects for metastatic colorectal cancer (mCRC) patients. Here, we report the updated results from RIFLE trial: the efficacy and safety of the combination of fruquintinib, PD-1 inhibitor tislelizumab and SABR in mCRC patients. Methods: This is a single-center, single-arm, prospective phase II clinical trial (NCT04948034). mCRC patients with at least 2 measurable lesions (≥1 of which can be targeted with radiation and ≥1 lesion outside the radiation field) who have failed ≥ 1L standard therapy will receive SABR followed by fruquintinib (5 mg, d1-14, qd) and tislelizumab (200 mg, d1, q3w) within two weeks from completion of radiation. The percentage change from baseline in the sum of longest diameter of target lesions, consist of specified radiated and non-radiated lesions, will be assessed after at least 2 cycles’ drug treatment. Primary endpoint is best objective response rate (ORR) of target lesions. Secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) rate, overall survival (OS) rate and toxicity. Results: From August 2021 to February 2024, 34 patients were included in the trial and 31 in the efficacy analysis. Median age was 62 years, 24 (77.4%) patients were male, 26 (83.9%) had ≥ 3 metastases, and 14 (45.2%) had received ≥ 3 prior lines of systemic therapy. The biological effective dose (BED) for irradiated lesions ranged from 37.5 to 105 Gy. Median study follow-up was 17.3 months (95%CI:13.841-20.759), 24 patients were alive and 13 remained on treatment. 1 patient achieved complete response (CR) for target lesions, 8 partial response (PR), 14 stable disease (SD), illustrating an ORR of 29% and a DCR of 74.2%. Median PFS was 8.8 months (95%CI:5.868-11.732). The most common treatment-related adverse events (TRAEs) were proteinuria (35.5%), hypertension (22.6%) and rash (19.4%). Grade 3-4 AEs occurred in 9 patients, including proteinuria and hypertension, and there were no treatment-related deaths. Conclusions: SABR combined with tislelizumab and fruquintinib shows promising effects and good safety in the treatment of metastatic colorectal cancer, which is expected to provide new therapeutic strategies and improve the prognosis for mCRC patients. Clinical trial information: NCT04948034 . [Table: see text]
Laparoscopic-assisted vs open surgery for low rectal cancer: 5-year outcomes of the LASRE randomized clinical trial.
Authors: Chi Pan , Jiang Weizhong , Su Xiangqian , Xu Jianmin , Qiu Huizhong , Kang Liang , Deng Haijun , Chen Weiping , Zhang Qingtong , Yang Chunkang , Guo Yincong , Zhong Ming , Ye Kai , You Jun , Xu Dongbo , Li Xinxiang , Ding Ke-Feng , Tao Kaixiong ,   LASRE Trial Investigators
Published: June 2024

e15630

Background: The long-term efficacy of laparoscopic versus open surgery for low rectal cancer has not yet been established. The primary outcome of 3-year disease free survival (DFS) have been published (Chi et al., ASCO GI 2024). Here, we presented the data of 5-year outcomes, including DFS and overall survival (OS) and locoregional recurrence. Methods: This is a multicenter, noninferiority trial. A total of 1070 patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery from November 2013 to June 2018. All analyses were performed on an modified intention-to-treat (mITT) basis. Results: The final analysis included 1039 patients (median age: 57 years, 620 men; 685 and 354 in laparoscopic and open groups, respectively). Clinical TNM stage was II/III in 659 patients, and I in the remaining 380 patients. The 5-year DFS rate was 76.4% in the laparoscopic group versus 75.6% in the open group (log-rank P = 0.766). The 5-year OS rate was 84.6% in the laparoscopic group versus 86.6% in the open group (log-rank P = 0.405). The 5-year locoregional recurrence rate was 5.5% and 3.1%, respectively (log-rank P = 0.079). Conclusions: The findings of the LASRE trial demonstrate that the noninferiority of laparoscopic surgery compared to open surgery for low rectal cancer, as evidenced by the 3-year outcomes, is sustained over a 5-year period when conducted by skilled surgeons. These results affirm laparoscopic surgery as a secure and minimally invasive option for the treatment of low rectal cancer. Clinical trial information: NCT01899547 .
AI-assisted colonoscopy in gastroenterology fellowship training: An interim analysis of a randomized controlled trial.
Authors: Kong Niwen , Chang Patrick , Nguyen Denis , Wang Sarah , Sharma Nisha , Amini Maziar , Ong Justin , Wang Daniel , Dodge Jennifer , Bruce Dara , Bui Aileen , Bakr Omar , Kim John , Buxbaum James
Published: June 2024

e15642

Background: Artificial intelligence (AI) assisted colonoscopy may increase adenoma detection rates (ADR) for endoscopists, but its role for trainees in learning endoscopy has not been delineated. This randomized control trial explores the impact of AI on ADR by year of fellowship and anatomical location. Methods: In a registered randomized controlled trial (NCT05423964), gastroenterology fellows were assigned to AI (GI Genius, Medtronic; Minneapolis, MN) vs. conventional colonoscopy(CC). We included all symptomatic or screening colonoscopies with adequate bowel prep by trainees (postgraduate year 4-6). Baseline demographics, polyp pathology, size in 5mm increments, and location, and ADR was collected and compared for AI versus CC arms. A multivariate regression was used to identify factors influencing ADR of the right colon. Results: Of 685 colonoscopies between March 15th to July 28th, 2023, a total of 381 procedures performed by 17 fellows met criteria. Patient characteristics were similar between arms. In the CC arm, there was no difference in ADR among fellow years (1st 39% vs. 2nd 33% vs. 3rd 36%, p = 0.63; Right colon: 1st 31% vs 2nd 21% vs 3rd 30%, P = 0.21). Within 2nd year fellows, there was higher ADR using AI vs. CC for screening colonoscopies (52% vs 17%, p = 0.025). In the right colon, ADR was significantly higher using AI vs. CC for screening alone colonoscopies within 1st and 2nd year fellows (1st 50% vs 13%, p = 0.04; 2nd 57% vs 9%, p < 0.001). 2nd year fellows also increased ADR in the right colon using AI vs CC for symptomatic and screening colonoscopies (44% vs 21%, p = 0.001). There was no difference in procedural time with addition of AI, but a trend to longer withdrawal time. Multivariable logistic regression analysis also showed AI assisted colonoscopies was associated with enhanced ADR in right colon for trainees performing colonoscopy for symptomatic and screening (OR [95%CI]: 2 [1.3-3.3]) and screening alone (OR [95%CI]: 8.3 [2.5-26.6]). Conclusions: This randomized control trial shows AI assisted colonoscopies improve ADR, particularly in the right colon for postgraduate trainees. We propose a use case for AI assisted colonoscopy guiding targeted improvement of ADR in in the right colon which has been highlighted by the American Gastroenterology Association as an area of need. Clinical trial information: NCT05423964 . [Table: see text]
Acute cardiac complications in colorectal cancer compared to other gastrointestinal malignancies: A 10-year retrospective study.
Authors: Olafimihan Ayobami Gbenga , Turk Ekrem , Jackson Inimfon , Bello Jeremiah , Olatunji Gbolahan , Kokori Emmanuel , Aderinto Nicholas , Oh Youjin , Fawehinmi Praise , Mullane Michael Russell
Published: June 2024

e15652

Background: Patients diagnosed with gastrointestinal (GI) cancers have long-term risks of cardiovascular disease and mortality. However, research comparing patients with colorectal cancer (CRC) to other GI cancers to assess their risk of acute cardiac complications is lacking. We evaluated the risk of hospitalization with acute cardiac complications (acute myocardial infarction [MI], arrhythmias and heart failure [HF]) among patients with CRC versus other GI cancers. Methods: A ten-year retrospective study using the Nationwide Inpatient Sample (NIS) database (2010-2019) was conducted. Using ICD-9 and ICD-10 codes, patients with diagnoses of GI cancers were identified. Multivariate logistic regression analysis was used to evaluate the odds of admission with an acute cardiac complication among patients with a diagnosis of CRC when compared to other GI cancers (esophageal, gastric, intestinal, hepatobiliary, and pancreatic cancers). Results: Among 4,408,321 GI cancer hospitalizations, 82,592 (0.18%) were for acute cardiac complications. Of these, 43.1% were in CRC patients and 56.9% were in those with other GI malignancies (P < 0.001). Multivariate analyses revealed that patients with CRC had more than two-fold higher odds of acute MI compared to other GI cancer patients (Adjusted Odds Ratio (AOR): 2.47; 95% Confidence interval ( CI): 2.30-2.65), 1.8 times higher risk of arrhythmia (AOR: 1.78; 95% CI: 1.69-1.87) and 2.2 times higher risk of HF (AOR: 2.23; 95% CI:2.11-2.36). Overall, in comparison to other GI cancers, CRC patients were twice as likely to be admitted for acute cardiac complications (AOR: 2.09; 95% CI:2.02-2.16). Conclusions: Colorectal cancer patients have significantly higher odds of hospitalizations with acute cardiac complications relative to other GI malignancies. Older age and pre-existing comorbidities of CRC patients are unlikely to sufficiently explain these findings. CRC patients would benefit from active surveillance for cardiac diseases as well as further research on the long-term survival impact of acute cardiac complications on CRC patients. [Table: see text]
Soluble guanylate cyclase activator vericiguat prevents anthracycline-mediated cardiotoxicity and sarcopenia through cGMP-NLRP3-cytokine pathway: Potential application in patients with cancer.
Authors: Iovine Martina , Quagliariello Vincenzo , Giacobbe Ilaria , Barbato Matteo , Giordano Vienna , Arianna Raffaele , Izzo Francesca , Berretta Massimiliano , Inno Alessandro , De Laurentiis Michelino , Maurea Nicola
Published: June 2024

e24015

Background: Anthracycline-induced cardiomyopathies and sarcopenia are frequently seen in cancer patients, affecting their overall survival and quality of life; therefore, new cardioprotective strategies are needed in cardioncology. Vericiguat is a new oral guanylate cyclase activator that reduces heart failure hospitalizations or cardiovascular death through improvement of smooth muscle cell relaxation and reduction of myocardial fibrosis and inflammation. In this study, we highlight on the potential cardioprotective properties of vericiguat against anthracycline.mediated cardiotoxicity and sarcopenia. Methods: Human cardiomyocytes (AC-16 cells) and Primary Skeletal Muscle Cells (HSkMC cells) were exposed for 24h h to doxorubicin (DOXO) at 0,3 and 1 µM with or withour a pre-treatment with Vericiguat at 0.1 or 1 or 10 µM for 1h. Mithocondrial cell viability, LDH and Citocrome C release were performed to study cytoprotective properties. TUNEL assay, cGMP and NLRP-3, Myd-88 intracellular levels were quantified through colorimetric and selective ELISA methods. IL-1β, IL-6, IL-8, CXCL-2, TGF-β and IL-18 were also analyzed in cardiac and muscle cell lysates after treatments. Results: Vericiguat exerts a significant cytoprotective and anti-apoptotic effect in cardiac and muscle cell lines during exposure to DOXO. A drastic increase in cGMP expression and reduction in NLRP-3, Myd-88 levels were also seen in Vericiguat-DOXO groups vs DOXO groups ( p < 0.001). Pro-inflammatory and cytotoxic cytokines were also downregulated after Vericiguat treatment during DOXO exposure. Conclusions: Vericiguat significantly reduced cardiotoxic effects and sarcopenia induced by DOXO therapy though enhancement of cGMP levels and reduction of NLRP-3/Myd-88/cytokines pathways. These findings provide a framework for future studies aiming to assess vericiguat for the primary prevention of anthracycline-mediated cardiotoxicity and sarcopenia.
Outcomes among hospitalized patients with colorectal cancer and comorbid congestive heart failure: A United States population-based cohort study.
Authors: Syal Arshi , Arya Yajur , Casipit Carlo , Wattanachayakul Phuuwadith , Casipit Bruce Adrian , Eidbo Sarah , Leighton John Charles , Dourado Claudia M.
Published: June 2024

e24019

Background: Colorectal cancer is one of the leading causes of cancer related deaths in the United States. Advances in chemotherapeutics have improved survival in these patients, although with the potential for more adverse effects. Congestive heart failure continues to be an important comorbidity in patients with colorectal cancer. However, its impact on outcomes in this subgroup needs further exploration. Methods: We utilized the 2020 National Inpatient Sample (NIS) Database in conducting this retrospective cohort study. We identified patients with colorectal cancer and congestive heart failure using appropriate ICD-10 diagnostic codes. We stratified patients with colorectal cancer based on the presence or absence of congestive heart failure. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of < 0.05 was considered statistically significant. The aim of this study was to investigate the impact of congestive heart failure on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charge among hospitalized patients with colorectal cancer. Results: We identified a total of 77130 hospitalized patients with colorectal cancer, of which 10.08% (7755/77130) had comorbid congestive heart failure. The overall in-hospital mortality among patients with colorectal cancer was 2.74% (2115/77130). Among those with comorbid congestive heart failure, the mortality rate was significantly higher at 6.5% (504/7755, p < 0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, congestive heart failure was found to be an independent predictor of increased in-hospital mortality (adjusted OR 1.79; 95% (confidence interval [CI], 1.33-2.41; p < 0.001), longer LOS (coefficient 2.42; CI 1.91-2.92; p < 0.001), and higher total hospitalization charge (coefficient $22464; CI $15132- $29795; p < 0.001). Conclusions: Our analysis demonstrated that congestive heart failure is widely prevalent in patients with colorectal cancer, and significantly worsens outcomes including increased in-hospital mortality, LOS, and cost of healthcare utilization. Early diagnosis and management of heart failure using guideline directed medical therapy along with close follow up may improve outcomes. Further prospective multicentric studies are warranted to better describe these associations.
Trends of stroke-related mortality among patients with cancer in the United States, 1999-2020.
Authors: Memon Roha Saeed , Nasir Muhammad Moiz , Mushahid Hasan , Farhan Syed Husain , Mahmood Umar , Mohiuddin Mubashir , Ahmed Jawad , Siddiqi Rabbia , Osama Muhammad , Farhan Syed Ali , Iqbal Abdul Ghani , Waqar Syed Hamza Bin , Riaz Shahid , Hamouda Danae M.
Published: June 2024

e24021

Background: Patients with cancer are at an increased risk of stroke and stroke-related mortality via various mechanisms such as hypercoagulability, direct tumor effects, and largely as side effects of treatments. Enhancement of thrombin release from chemotherapy induced release of extracellular vesicles and cell-free DNA, and the use of angiogenesis inhibitors are some of the proposed mechanisms for stroke development in patients with cancer. Despite this, current guidelines lack clarity in identifying patients with cancer as having moderate to high risk of mortality from stroke. Recognizing this complex relationship is pivotal for crafting comprehensive care plans that address the dual challenges of cancer and stroke risks. Hence, our CDC analysis focuses on unraveling mortality trends among patients grappling with both conditions from “1999 to 2020”. Methods: We analyzed national mortality data from the multiple causes of death files in the CDC WONDER database from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 people were calculated for the total population, stratified by gender, race, urban/rural metro status, and census region. Annual percent change (APC) was calculated using the Joinpoint regression software. Results: A total of 36,648 stroke-related deaths among patients with cancer occurred between 1999 and 2020. The APC trends are as follows: a major decrease of -6.8 (95% CI: -11.8 to -1.5) from 2002 to 2009, a slight decline of -1.23 (95% CI: -13.8 to 13.2) from 2009 to 2014, a significant decrease of -6.71 (95% CI: -46.2 to 61.7) from 2014 to 2017, and an increase of 2.07 (95% CI: -26.1 to 41.1) from 2017 to 2020. Men consistently showed higher mortality rates compared to women in 1999 (AAMR Men: 1.0 vs Women: 0.63) and 2020 (AAMR Men: 0.94 vs Women: 0.69). Moreover, when stratified by race non-hispanic (NH) Black showed the highest mortality rate, followed by NH Whites, and Hispanics throughout the study period between 1999 (AAMR NH Black: 0.96 vs NH White: 0.75 vs Hispanic: 0.32) and 2020 (AAMR NH Black: 0.85 vs NH White: 0.81 vs Hispanic: 0.53). Rural areas compared to urban areas showed consistently higher mortality rates over the study period. Conclusions: Despite more than a decade-long decline, stroke-related mortality among cancer patients has significantly increased since 2015. Targeted therapy and investigations into the role of social determinants of health may improve care for these patients. Further investigation is warranted to elucidate the mechanisms for the increase in stroke-related mortality among people with cancer, particularly those with the following demographics: Men, Black or African American, and residents of rural areas and Midwestern regions.
Prevalence and clinical outcomes of acute heart failure among patients with mediastinal radiation exposure: A propensity score matched analysis.
Authors: Bekoju Kanchhi , Kansakar Sajog , Shikhrakar Shreeja , Guragain Ashish , Chudy-Onwugaje Dilichukwu , Winn Soe
Published: June 2024

e24029

Background: Radiation therapy (RT) for malignancy in mediastinal region is associated with radiation-induced heart disease in subsequent years, including coronary, valvular, myocardial, pericardial and conduction system disease. Although increased risk of diastolic heart failure (DHF) has been established, there is limited data on the prevalence, trends and outcomes of acute DHF admissions in patients with prior mediastinal RT. Methods: We extracted data from the National Inpatient Sample (NIS) Database from 2016 to 2020. We included all admissions ≥18 years old with a principal diagnosis of acute DHF with and without history of RT for mediastinal cancer using International Classification of Diseases Tenth Revision (ICD-10) codes. Propensity score matching was performed to balance hospital characteristics, patient demographics and comorbidities between the two groups. Univariate logistic regression was performed in the balanced cohorts. The primary outcome was inpatient mortality. Analysis was performed using STATA-MP, version 14.2. Results: A total of 2,356,025 admissions for acute DHF were identified between 2016 to 2020, of which 15,435 (0.65%) had prior mediastinal RT. During the study period, we found an increasing trend in the number of admissions for acute DHF (p trend < 0.01) along with an increased proportion of patients with prior mediastinal RT. (0.55% in 2016 to 0.78% in 2020, p trend < 0.01). After propensity score matching, there was no difference in in-hospital mortality (odds ratio [OR] 1.12, 95% CI 0.79-1.58, p = 0.537), or complications such as cardiogenic shock, respiratory failure, stroke, venous thromboembolism, or acute kidney injury between the two cohorts. There was no difference in length of stay, however, cohort with history of mediastinal RT had higher hospital charges ($26,634 vs $31,511, p < 0.01). Conclusions: Exposure to mediastinal RT represents a minority but growing number of hospital admission with DHF. The mortality and complications of RT associated DHF does not differ significantly from those with traditional etiologies of DHF.
Chemotherapy in the last 30 days of life, correlation with age and palliative care referral: A 1-year retrospective gastrointestinal program experience at SQCCCRC.
Authors: Ghoche Ahmad , Abu Omar Rami , Mahmoud Amani Ismail , Al-Moundhri Mansour
Published: June 2024

e24038

Background: Chemotherapy in the last days of life can carry unnecessary toxicities to the patient with no significant impact on survival and disease outcome. This is becoming of greater interest with the involvement of palliative care in patient’s management along with the advent of new therapeutic options with progressively increased cost of treatment. Methods: In our retrospective study, we aimed to analyze retrospectively the data of GI tumors treated at SQCCCRC over one year, by looking at the possible factors influencing the time from last treatment to death. We conducted chart review of all death that occurred between January 2023 and December 2023 in the GI cancer program at SQCCCRC. Information on demographics, type of GI cancer, type, intent and route of chemotherapy, line of chemotherapy and referral to palliative care were collected. Results: A total of 65 patients died within the GI cancer program between January 1st, 2023, to dec 31st, 2023. Most (72.7%) of the patients died of disease progression. Intent for chemotherapy was palliative in 90.9% of cases. Chemotherapy was parenteral (Intravenous) for the majority (60%, 38/63) of the patients. From all the recovered deaths, a total of 52 patients (82%) were referred to palliative team before death whereas palliative team was involved in the journey of all patients. 12 deaths out of 65 occurred in ICU. Only 11 out of 65 patients died within last 30 days of treatment: 81.8% of them were under palliative care at the time of death. For this group, the median age at diagnosis was 50 yo. Median age at death was 61 yo. 72.7% were male. Primary site of disease was colon followed by stomach. Median time from diagnosis to palliative referral was 13.5 months. 8 patients died within 3.5 days of referral to palliative care. In the logistic regression models, only age at diagnosis was a significant predictor for receiving chemotherapy in the last 30 days of life (p = 0.019). Older age was associated with lower odds of receiving chemotherapy in this period (OR = 0.94, 95% CI = 0.89-0.99). Referral to palliative chemotherapy was not associated with decreased rate of treatment administration within last 30 days of life. Conclusions: While some real-world data suggested correlation between shifting to palliative care and administration of chemotherapy in the last 30 days of life, this was not the case in our collected sample, and only the age of the patient played a role in the chemotherapy timing before death. Further studies are needed to study the reasons behind and the best way to improve patient’s centered approach.
A comprehensive analysis of portal vein thrombosis in malignancy.
Authors: Prasad Apurwa , Bartock Matthew Tyler , Gyawali Mallika , Acharya Anamol , Bhattarai Shweta , Hotwani Priya
Published: June 2024

e24042

Background: Portal vein thrombosis (PVT) is a rare venous thromboembolism, is often linked to cirrhosis, infection, and malignancy. Advancements in imaging have noted an increasing incidence of PVT, particularly in solid cancers. Treating PVT with malignancy is challenging due to lack of data, poor recanalization, and substantial bleeding risk with anticoagulation. This study aims to enhance understanding of malignancy-related PVT, anticoagulation trends, and assess prognosis. Methods: We conducted a multicenter, observational retrospective analysis of patients diagnosed with PVT (ICD code 452,181) from 2013 to 2023. Inclusion criteria: age > 18 and acute portal vein thrombosis. Exclusion criteria: presence of tumor thrombosis, and thrombus in other splanchnic vessels (e.g., mesenteric vein). Data entry was performed on a study-specific REDCap database. Patients with concomitant malignancy were identified and further assessed for cancer type, anticoagulation use, bleeding outcomes, and prognosis. Proportion analysis using Z test was done to compare outcomes between groups. Results: In our study of 583 patients, 236 (40.48%) had concurrent malignancy, predominantly male (144, 61.01%),and female (92, 38.98%) mean age 65. Common malignancies included HCC (28.38%), pancreatic (24.15%), colo-rectal (11.86%), cholangiocarcinoma (8.47%), myeloproliferative neoplasm, prostate, and gynecological cancers each (2.96%), and other cancers (18.22%). 41% had metastasis to liver. Cirrhosis was present in 40%, particularly in HCC patients (89%). Of the total,163 (69%) received anticoagulation; 26.38% showed improvement or re-canalization within a year. The primary anticoagulants were Direct Oral Anticoagulants (DOACs) (57%), with an increasing trend in the last 5 years (69.44%), followed by Low-Molecular-Weight Heparin (LMWH) (19%) and warfarin (14%). Most patients initiated on heparin infusion (9.81%) transitioned to hospice care. Bleeding events in patients receiving DOAC versus LMWH + Warfarin were 36.55% and 33.33%, respectively (p = 0.69). Patients without anticoagulation demonstrated a higher one-year mortality compared to those with anticoagulation (83.56% vs. 63.19%, p value < 0.05). Overall,malignancy-associated PVT had a significantly higher case fatality rate than non-malignancy cases, regardless of anticoagulation (81.35% vs. 32.85%, p < 0.05). Conclusions: There is a significant association between malignancy and PVT, particularly in HCC and pancreatic cancer. The increased mortality in malignancy-related PVT emphasizes the critical role of anticoagulation, which has demonstrated efficacy in improving outcomes, including one-year mortality. Although DOACs have seen increased use in the last 5 years, bleeding events have remained comparable. Further research is warranted to explore patient selection for optimal anticoagulation strategies.
Safety and efficacy of low dose versus high dose corticosteroid for graft versus host disease (GVHD): A systematic review.
Authors: Khanal Pradeep , Shah Sangam
Published: June 2024

e24047

Background: Graft-versus-host disease (GVHD) is an immune-mediated complication of allogeneic hematopoietic stem cell transplantations. Current standard dose of corticosteroids used by the most hospitals for GVHD patients is 1-2 mg/kg/day. The prednisone dose used in the treatment of a GVHD has been a matter of debate. In this systematic review, we aimed to compare low dose prednisone to high/standard dose prednisone in terms of multiple prognostic outcomes of the patients undergoing allogenic hematopoietic stem-cell transplantations. Methods: We searched the databases PubMed, Cochrane library, and clinicaltrials.gov for all studies investigating the efficacy and safety of low dose and high dose steroid for GVHD. We set the search strategy incorporating the search terms, Graft-versus-host disease," "low dose cortico-steroid," and "high dose corticosteroid", and operated using the Boolean operators ‘AND’, and ‘OR’. Thus, retrieved articles were then exported on an Excel sheet, and duplicates were removed. After selecting the study based on inclusion criteria, data on study characteristics and biomarker description was extracted on a pre-determined data extraction table on the Microsoft Excel. Results: The search revealed 547 studies and 3 studies that met the eligibility criteria of this review have been included.During relapse, chronic GVHD, mortality, and malignancy outcomes were generally similar between doses, low-dose prednisone showed benefits for leukemia-free, relapse-free, and overall survival. Overall, the randomized trial by Chang et al. found lower risks of HZV and pulmonary infections with low-dose prednisone compared to standard-dose. (Table 1) Other infections were similar between groups. Conclusions: Low-dose prednisone showed similar efficacy to standard-dose for most GVHD outcomes (relapse risk, mortality), with potential benefits on survival, reduced HZV/pulmonary infections, and reduced adverse effect of higher cumulative dose of corticosteroids. [Table: see text]
HRQoL in patients with GBM: The impact of tumor treating fields.
Authors: Patel Drashti , Thakkar Rajvi , Fleeting Chance , Ghiaseddin Ashley Parham
Published: June 2024

e24049

Background: Glioblastoma (GBM) is the most common malignant glioma with a dismal prognosis. Patients experience a range of progressively worsening symptoms, including headaches, nausea, seizures, and cognitive deficits throughout their disease course. Initial treatment for newly diagnosed patients consists of maximal safe surgical resection followed by fractionated radiation treatment with concomitant temozolomide. Presently, there are two approved adjuvant treatment modalities following chemoradiation: temozolomide and tumor-treating fields (TTFields). In this poster, we explore the impact of TTFields on the quality of life, assessed through health-related quality of life (HRQoL), in patients with GBM. Methods: Using PubMed, Medline-indexed articles were collected using this structured query: Glioblastoma[MeSH] AND (("Electric Stimulation Therapy*"[MeSH]) OR ("Transcranial Direct Current Stimulation*"[MeSH]) OR "Tumor Treating Fields" OR "TTF") NOT "RAT" This yielded 233 results before the search date (2023). Collected sources were uploaded to Covidence to allow for multi-reviewer screening, review, and extraction. For completeness, limited forward and back citations using the ResearchRabbit tool and limited addition of non-Medline indexed articles via unstructured query yielded four additional results. Sources were filtered by study type and included/excluded based on accessibility, sample population, design, outcome measures, and interventions. Five randomized control studies remained. From this subset, bias, effect size, I2-index, and forest analysis with random effect model estimation were calculated. Results: Data analysis showed that TTFields therapy has demonstrated associations with increased progression-free survival and enhanced overall survival rates without negative effects on HRQoL. Some patients have reported improvement in mobility, self-care, and carrying out regular activities. One notable side effect observed in these patients was increased skin itchiness, which was expected due to the use of transducer arrays. Conclusions: This project identified a research gap in standardizing the assessment of quality of life in patients treated with TTFields. A significant limitation in research on TTFields is an overall lack of HRQoL data, often due to patients failing to follow-up with surveys. Future research should prioritize patient follow-up to obtain more comprehensive and precise longitudinal data on HRQoL while considering disease and treatment characteristics.