bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of patients with peritoneal carcinomatosis treated with HIPEC and chemotherapy or HIPEC alone: A single center community experience.
Authors: Huber Benjamin Michael 
Published: June 2024

e15578 Background: Peritoneal carcinomatosis is a common presentation of intraperitoneal malignancies. The optimal management of peritoneal carcinomatosis is currently unknown but can contain a combination of HIPEC and chemotherapy. Optimal timing and order of these interventions is controversial. HIPEC surgery alone can provide a cure rate of approximately 16% with macroscopically complete resection. The PRODIGE 7 trial demonstrated no difference in overall survival between HIPEC plus cytoreduction versus cytoreduction alone with six months of systemic chemotherapy. Which patients should receive HIPEC, chemotherapy and HIPEC or chemotherapy alone remains unknown. Methods: This is a single center, retrospective chart review assessing all patients age 18 and above who received HIPEC surgery with and without the administration of chemotherapy at Ascension Saint John Hospital. Results: We found that there was no significant difference in overall survival and progression free survival between the HIPEC and HIPEC with chemotherapy group with a OS of 57.2 months and 52.5 months; and PFS of 33.6 and 34.4 months respectively. We found that patients with a PCI score between 0 and 13, overall survival favored the HIPEC alone group versus the HIPEC with chemotherapy with a p value of 0.043. There was no difference in progression free survival and overall survival in all other groups when stratified by PCI. When stratified by disease subtype, we no differences between PFS and OS for both appendiceal and colon cancer. Conclusions: The primary objective of this study was to investigate the difference in overall survival and progression free survival among patients with peritoneal carcinomatosis when treated with either HIPEC with systemic chemotherapy versus HIPEC alone. This analysis among 100 patients showed no statistically significant differences in OS or PFS for patients receiving a combination of HIPEC with systemic chemotherapy versus HIPEC alone. The only exception to this was with respect to OS in patients with a PCI score between 0-13. In this group, 0 patients in the HIPEC along group experienced disease progression where 5 progressed in the HIPEC and chemotherapy group. Our data suggests that HIPEC alone may be a reasonable treatment approach for patients with a low PCI score. Important conclusions can be drawn from the data when compared to historical trials. The PROTEGE 7 study found that the median overall survival was approximately 41.7 months for the HIPEC and cytoreductive surgery group and 41.2 months versus cytoreductive surgery alone. The overall survival for the HIPEC alone group was 57.2 months and 52.5 months for the HIPEC plus chemotherapy group. This data suggests that the combination of HIPEC and chemotherapy is a reasonable approach to patients with peritoneal carcinomatosis.
The impact of socioeconomic status on gastrointestinal cancer care delivery in southeast Texas.
Authors: Abdelhakeem Ahmed , Anwar Junaid , Thompson Jacob , Terro Telice , Henry Sara , Blevins Samantha , Vasefi Maryam 
Published: June 2024

e15579 Background: Gastrointestinal (GI) cancers are a leading cause of cancer deaths in the US with an estimated 1,038,410 new cases and a 30.4% mortality rate in 2023. Disparities in cancer care are well documented and result from several variables, including socioeconomic status (SES), behavioral, and biological factors. We conducted a retrospective population-based cohort study aimed to investigate the relationship between various socioeconomic factors and delays in cancer treatment initiation, emphasizing the impact of gender, race, age, and geographical distance on the time to treatment initiation (TTI). Methods: We identified patients with colorectal, hepatobiliary, small intestinal, and gastroesophageal cancers, who received their cancer diagnosis and initiated treatment at Baptist Hospitals of Southeast Texas in Beaumont, Texas between January 2012, and December 2017. SES data, including age, sex, race, geographical distribution, insurance status, cancer staging, and treatment were collected. Logistic regression was performed to determine risk association by calculating odds ratios with 95% confidence intervals, as well as p-values to determine significance. The primary outcomes of interest were the overall survival (OS) rate, and TTI defined as the time interval between the confirmed cancer diagnosis and initiating the first treatment modality. Results: A total of 517 GI cancer patients were included in this study, with 359 comprising a cohort of patients with colorectal cancer. The majority of patients included were ; caucasians(%) males (%).. African American patients were significantly more likely to receive delayed treatment, Odds Ratio (OR): 5.89, 95% confidence interval (CI) 4.02-8.62, especially compared to the odds for similar Caucasian patients (OR: 0.16, CI: 0.11-0.23). When compared to younger counterparts, patients above the age of 80 were found to have poorer odds of prolonged survival (OR: 2.91, CI: 1.80-4.72). Patients who lived 30 miles away or further from our hospital had longer TTI compared to those living within 30 miles radius (OR: 1.85, CI: 1.19-2.87), a risk which remained significant within the colorectal cancer cohort (OR: 2.20, CI: 1.29-3.74). Patients with Medicare insurance showed longer TTI (OR: 1.50, CI: 1.01-2.23), and decreased OS (OR: 1.79, CI: 1.05-3.06)). No statistically significant difference was observed based on gender. Conclusions: Age, geographical location, and racial SES variables contribute to the disparities in GI cancer care in our community. Addressing these disparities and implementing targeted interventions to mitigate the impact of socioeconomic barriers is imperative to ensure equitable access to timely and effective cancer care, ultimately leading to improved patient outcomes and cancer survival rates.
Circulating tumor DNA (ctDNA) kinetics in colorectal cancer (CRC) treated with curative intent in the VICTORI study with an ultrasensitive MRD assay.
Authors: Solar Vasconcelos Joao Paulo , Titmuss Emma , Navarro Fabio , Abbott Charles , Chia Brendan , Topham James T. , Ladua Gale , Krishnan Tharani , Hegebarth Daniela , Lim Howard J , Gill Karamjit , Gill Sharlene , Brown Carl J. , Ghuman Amandeep (Anu) , Meneghetti Adam , Renouf Daniel John , Schaeffer David F. , Chen Richard , Boyle Sean Michael , Loree Jonathan M. 
Published: June 2024

e15625 Background: Detection of molecular residual disease (MRD) with ctDNA is highly prognostic for recurrence in CRC. However, many cancers still recur without detectable ctDNA and increased lead time before clinical recurrence may create a window of opportunity to intervene. Here we apply an ultra-sensitive assay, NeXT Personal, to profile patients in the VICTORI study, a prospective cohort of patients with CRC managed with curative-intent treatment. Methods: To date, the first 33 patients with CRC have undergone panel creation. NeXT Personal was employed to construct personalized liquid biopsy panels for each patient with up to ~1,800 single nucleotide variants (SNV) identified via whole-genome sequencing. For each patient, plasma is collected before curative intervention (baseline), every 2 weeks for 2 months (MRD window), and every 3 months for up to 3 years (surveillance). VICTORI will enroll > 175 patients and include a health economics analysis. Results: Of 33 patients enrolled to date, 25 (76%) are stage I-III and 8 are stage IV treated with curative interventions. 18 colon cancers and 15 rectal cancers are included. Pre-operative baseline sensitivity was 90.6% (29/32; 1 patient excluded as pCR at the time of baseline blood draw). Of the MRD- patients at baseline, 2 had prior neoadjuvant treatment and 1 was stage 1. Preliminary results (median 7.2 month follow-up; 5 recurrences) show 80% (4/5) of recurrences are MRD+ at the 4-week landmark and 50% (2/4; 1 missing sample) were MRD+ at the 2-week landmark. In 75% (3/4) stage II-III recurrences, the first MRD+ detection was in the ultra-low range of < 100 PPM ( < 0.01% tumor fraction). MRD detection at week 4 and 8 trended towards poorer recurrence-free survival (RFS) with similar separation of patients (log rank p = 0.062 and p = 0.011, respectively). Conclusions: Preliminary results from our prospective study demonstrate strong rates of ctDNA detection at week 4 landmark analysis, potentially due to detection of very low levels of ctDNA with an ultra-sensitive MRD assay. The majority of the first detections for MRD were in the ultra-low ctDNA range, indicating the importance of high sensitivity MRD testing. [Table: see text]
A GWAS in Swedish colorectal cancer families with gastric and prostate cancer.
Authors: Samola Winnberg Johanna , Vermani Litika , Liu Wen , Soller Veronika , Thutkawkorapin Jessada , Lindblad Mats , Lindblom Annika 
Published: June 2024

e15644 Background: We have previously suggested a syndrome with increased risk for colorectal- and other cancers, primarily gastric- and prostate cancer. The data favoured this syndrome inherited as a complex disease. Therefore, we conducted a Genome Wide Association Study (GWAS) on colorectal cancer patients, who’s relatives had prostate-, and/or gastric cancer. Methods: The GWAS analysis consisted of 685 cases of colorectal cancer and 4780 healthy controls from Sweden. A sliding window haplotype analysis was conducted using a logistic regression model.Thereafter, we performed sequencing to find candidate variants, finally to be tested in a nested case-control study. Results: Candidate loci/genes on ten chromosomal regions were suggested with odds ratios (ORs) between 1.71-3.62 and p-values < 5x10-8 in the analysis. The regions suggested were 1q32.2, 3q29, 4q35.1, 4p15.31, 4q26, 8p23.1, 13q33.3, 13q13.3, 16q23.3 and 22q11.21. All regions, except one on 1q32.2, had protein coding genes, many already shown to be involved in cancer, such as ZDHHC19, SYNPO2, PCYT1A, MYO16, TXNRD2, COMT, and CDH13. Sequencing of 122 colorectal cancer patients with gastric- and prostate cancer in their families identified 10 candidate variants from six of the loci in the haplotype regions to finally be tested in a nested case-control study of similar colorectal cancer cases and controls. Conclusions: There was some support for an increased risk of colorectal-, gastric-, and/or prostate cancer in all the six loci tested. [Table: see text]
Effect of combinatorial immune checkpoint blockade on myocardial expression of NLRP-3 and secretion of H-FABP, NT-Pro-BNP, interleukin-1β, and interleukin-6: Biochemical implications in cardio-immuno-oncology.
Authors: Paccone Andrea , Quagliariello Vincenzo , Passariello Margherita , Iovine Martina , Bisceglia Irma , Ascierto Paolo Antonio , Inno Alessandro , Maurea Fabrizio , Giacobbe Ilaria , Berretta Massimiliano , Giordano Vienna , Izzo Francesca , Barbato Matteo , Arianna Raffaele , De Lorenzo Claudia , Maurea Nicola 
Published: June 2024

e24016 Background: Immune checkpoint blockade in monotherapy or combinatorial regimens with chemotherapy or radiotherapy have become an integral part of oncology in recent years. Monoclonal antibodies against CTLA-4 or PD-1 or PDL-1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA in combination with Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study in association with Ipilimumab for therapy of metastatic lung cancer. Myocarditis, vasculitis and endothelitis are rarely observed in these patients on monotherapy, however new combination therapies could expose patients to more adverse cardiovascular events. Methods: human cardiomyocytes, human peripheral blood lymphocytes (hPBMCs) and combinatorial ICIs (PD-L1 and CTLA-4 or PD-1 and LAG-3 blocking agents, at 100 nM) for 48 h. After treatments, cardiac cell lysis and secretion of biomarkers of cardiotoxicity (H-FABP, troponin-T, BNP, NT-Pro-BNP), NLRP3-inflammasome and Interleukin 1 and 6 were determined through colorimetric and enzymatic assays. Mitochondrial functions were studied in cardiomyocyte cell lysates through quantification of intracellular Ca++, ATP content and NADH:ubiquinone oxidoreductase core subunit S1 (Ndufs1) levels. Histone deacetylases type 4 (HDAC-4) protein levels were also determined in cardiomyocyte cell lysates to study potential epigenetic changes induced by immunotherapy regimens. Results: Both combinations of immune checkpoint inhibitors exert more potent cardiotoxic side effects compared to monotherapies against human cardiac cells co-cultured with human lymphocytes. LDH release from cardiac cells was 43% higher in PD-L1/CTLA-4 blocking agents, and 35.7% higher in PD-1/LAG-3 blocking agents compared to monotherapies. HDAC4 and intracellular Ca++ levels were increased, instead ATP content and Ndufs1 were reduced in myocardial cell lysates (p < 0.001 vs untreated cells). Troponin-T, BNP, NT-Pro-BNP and H-FABP, were also strongly increased in combination therapy compared to monotherapy regimen. NLRP3 expression, IL-6 and IL-1β levels were also increased by PDL-1/CTLA-4 and PD-1/LAG-3 combined blocking agents compared to untreated cells and monotherapies. Conclusions: Data of the present study, although in vitro, indicate that combinatorial immune checkpoint blockade, induce a pro- inflammatory phenotype, thus indicating that these therapies should be closely monitored by the multidisciplinary team consisting of oncologists, cardiologists and immunologists.
Investigation of cardiotoxicity with concomitant use of anthracyclines and checkpoint inhibitors.
Authors: Mazloom Anita , Asturias Jose Alejandro , Manan Haris , Prodduturvar Pranitha 
Published: June 2024

e24022 Background: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment and currently are the standard of care for early stage triple negative breast cancer in combination with anthracyclines (AC). It is known that both ICI and AC carry risk of cardiotoxicity. Studies have also shown that there is increased risk of cardiotoxicity with dual ICI. However no studies have evaluated the risk with concomitant use of ICI and AC. Here we investigated if there is increased cardiotoxicity risk with this combination regimen in a retrospective study. Methods: We did a retrospective analysis of patients with stage II and stage III triple negative breast cancer treated with combined AC and ICI at University of South Alabama Mitchell Cancer Institute Mobile, AL from January 2020 until June 2023. Data included demographics, cardiovascular (CV) risk factors and treatment. CV risk factors were detailed from 2022 ASCO guidelines. Echocardiograms were used to evaluate left ventricular ejection (LVEF). Therapy related cardiovascular toxicity was defined by ESC guidelines 2022 as any new decrease in LVEF to < 40% or any decrease in LVEF < 50% and 10 percentage points decrease from baseline. Adverse events (AE) and risk analysis were calculated. Results: Of the total 49 patients, all were female with a mean age of 53 years old (30-82). 55% of patients had less than 2 CV risk factors (n = 27) and 45% had more than 2 (n = 22). 84% completed all 4 cycles of neoadjuvant AC course without dose adjustment. The median number of cycles of Pembrolizumab was 12 with a range of 7 to 17 cycles including adjuvant Pembrolizumab. All patients had a baseline echo with LVEF > 55%. Two patients (0.04%) developed cardiotoxicity. One patient had LVEF that decreased to EF 45-50% while on surveillance. Another patient developed myocarditis during treatment with EF 25-30% and died from cardiogenic shock. Both patients had 2 CV risk factors and were African American. Only 24% (n = 12) had surveillance echocardiograms completed one year post treatment. Conclusions: Our study results showed that cardiotoxicity risk was lower compared to that in the Keynote-522 trial. The outcomes are limited as a majority (76%) of the patients did not have surveillance echos completed. While the risk of cardiotoxicity with ICI and AC have been studied independently, there have been mouse models that showed that AC therapy may make heart vulnerable to toxicity from ICI therapy. To our knowledge, this is the first study to evaluate cardiotoxicity in patients who received concomitant AC and ICI treatment. Our study highlights the importance of prospective studies and long term follow up to monitor cardiotoxicity in these patients as early detection is key to prevent future morbidity. [Table: see text]
Cardiovascular toxicity of fluoropyrimidines: Experience from a quaternary referral center.
Authors: Chedid El Helou Michel , Laderian Bahar , El Hajjar Abdel Hadi , Mushtaq Ali , Sadler Diego , Moudgil Rohit , Griffin Brian , Collier Patrick 
Published: June 2024

e24028 Background: Fluoropyrimidines, including 5-fluorouracil (5-FU) and capecitabine, are widely used chemotherapeutic agents. Their use has been linked to various forms of cardiovascular (CV) toxicity. We sought to analyze the rate of CV events and associated factors in patients receiving fluoropyrimidines at our institution. Methods: We included all patients who received intravenous 5-FU or oral capecitabine at the Cleveland Clinic since 2000. Diagnosis data was obtained based on ICD-10 Codes. CV events included chest pain/angina, myocardial infarction, chronic ischemic heart disease, arrhythmias, conduction disorders, cardiac arrest, cardiomyopathy, and heart failure. CV events were accounted for if they occurred during treatment or within 30 days following the latest administration of the agent. Logistic regression was performed to identify predictors of CV events. Results: A total of 17,236 patients were included, of which 9,386 (54.5) received 5-FU and 7,850 (45.5) received capecitabine. Median age at treatment was 63. The most frequent malignancies were gastrointestinal (70%) and breast cancer (12.3%). A total of 2,283 patients (13.2%) experienced at least one CV event either during treatment or within 30 days following drug administration. The most frequent CV events were chest pain/angina (35.7% of all events). On multivariable logistic regression, factors associated with increased risk of CV events were black race, smoking history, hypertension, and obesity (Table). A prior history of CV disease was also associated with increased risk of CV events (OR 1.22; 95% CI [1.09 - 1.33]). Finally, intravenous 5-FU was linked to higher odds of CV events compared to oral capecitabine (OR 1.48; 95% CI [1.34 - 1.63]). Conclusions: This large-scale cohort study provides pivotal insights into the cardiovascular risks associated with fluoropyrimidine therapy. Besides traditional risk factors, black patients were more likely to suffer from CV events. Additionally, capecitabine may offer better CV outcomes compared to 5-FU. These findings underscore the need for refined risk assessment and enhanced cardiovascular monitoring in patients treated with fluoropyrimidines. [Table: see text]
End of life treatment in gynecological cancers in an integrated care model: A single institution experience from Oman.
Authors: Zribi Aref , Faisal Abdellatif Ahmed Amnah , Al-Sayegh Hasan , A Burney Ikram 
Published: June 2024

e24036 Background: The use of chemotherapy closer to the end of life (EOL) and the optimal time of initiating palliative care interventions are subjects of ongoing debate. In a traditional care model (TCM), the institution of EOL care is a complex decision-making process, that involves patient, family members, and the oncologist, and involves transfer of patients from one to the other service. Integrated care model (ICM) is a newer concept, is designed around the needs of the patients, and may have the potential to improve quality of life and reduce the cost of healthcare towards EOL. At our center, we work in ICM in organ-based clinical programs and report the use of systemic treatment in patients with gynecological cancers (GC) nearing EOL. Methods: We analyzed retrospectively the use of chemotherapy and other systemic cancer-directed therapies in patients with GC, who died between Sept 2021 and December 2023 at a single institution. Information on the cancer-type, intention of treatment, and the time between last treatment and death was obtained from electronic patient records (EPR). Results: Over the study period, a total of 22 patients passed away. All patients received palliative care as part of the integrated care. All patients had been declared ‘not for resuscitation’ before death. Twelve patients had ovarian cancer, 5 had endometrial cancer, 4 had cancer of cervix, and one had vulvar cancer. The median age at diagnosis was 53 years (29-80). The systemic treatment was 1st line in 5 patients (23%), 2nd line in 8 patients (36%), and 3rd or more line in 6 patients (27%) respectively. Three patients (14%) did not receive any cancer-directed treatment (aged 80, 71 and 61). The ultimate line of treatment was cytotoxic chemotherapy for all patients, except for one who received Olaparib, and one who received trastuzumab with chemotherapy. There was no treatment-related mortality. The median time from last treatment to death was 55 days. Of the 19 patients who received treatment, 6 patients (32%) received treatment in the last 30 days, 5 between 30 and 60 days (26%), 5 between 60 and 90 days (26%), and 3 more than 90 days before death. Four patients died at home. Age at diagnosis (51 vs 55 years), age at death (51.5 vs 57.5 years), or time from diagnosis to death (11.5 vs 22 months), did not predict whether patients received treatment within the 30 days of death or earlier. Conclusions: All patients received palliative care as part of integrated cancer care. The ICM may have led to lower use of cancer treatment near EOL. The data may provide a benchmark for the region.