tbuckley/cabot-search huggingface dataset:
Effect of nurse-led multi-disciplinary treatment on patients with head and neck tumors: A randomized controlled trial.
Authors: Jingjing Wang, Lei Cai, Yiyan Pei, Juejin Li, Zhigong Wei, Ruidan Li, Yonglin Su, Xiaolin Hu, Xingchen Peng
Journal: Journal of Clinical Oncology (2024)

12013 Background: Patients undergoing radiotherapy (RT) for head and neck tumors are prone to experiencing nutritional and psychological issues as a result of adverse events to the treatment, which may ultimately lead to radiotherapy interruption (RTI). We conducted a prospective, randomized controlled trial to assess the effect of nurse-led multi-disciplinary treatment (MDT) interventions, incorporating psychological and nutritional interventions, on RTI rates and quality of life (QoL) among patients undergoing RT for head and neck tumors. Methods: Patients with head and neck cancer undergoing RT at West China Hospital, Sichuan University were enrolled. Eligible patients were randomly assigned in a 1:1 ratio to receive either the standard oncology care (standard group) or the nurse-led, whole-course MDT care (MDT group). The MDT care included nutritional and psychological interventions provided by a team of a radiotherapist, an oncology specialty nurse, a dietitian, a psychotherapist and a rehabilitation therapist. The primary end point was RTI rate in the per-protocol set (PPS). Patients’ QoL was assessed using the EORTC QLQ-C30 and EORTC QLQ-H&amp;N35 questionnaires. Nutritional status was assessed using NRS 2002 and PG-SGA, and psychological status was assessed using DT, PHQ-9 and HADS. Results: A total of 233 patients were enrolled in the study. At the final follow-up, 112 patients in the standard group and 114 patients in the MDT group completed all follow-up assessments. The RTI rate in the MDT group was significantly lower than that in the standard group (MDT vs. standard: 11.4% vs. 25.9%, P= 0.005). Differences in QoL among patients favored MDT care over standard care, particularly in emotional function, GHS, fatigue, and insomnia. Baseline patients’ nutritional and psychological status were similar between two groups. From mid-RT to 6 months after RT, the nutritional and psychological status of patients in the MDT group improved at certain follow-up points compared with the control group. The rehospitalization rate in the MDT group was significantly lower than that of control group (MDT vs. standard: 7.9% vs. 18.8%, P= 0.016). Conclusions: Nurse-led MDT interventions effectively reduces RTI, improves nutritional status of patients, and alleviates their psychological burden, making it a worthy approach for dissemination in developing countries. Clinical trial information: NCT05828004 .
Fasting mimicking diet reduces anti-OX40/anti PD-L1 and anti-PD-1/anti-CTLA-4 cardiovascular side effects in preclinical melanoma models.
Authors: Vincenzo Quagliariello, Salvatore Cortellino, Gloria Delfanti, Annabella Di Mauro, Fabiana Tatangelo, Vanessa Spagnolo, Euplio Visco, Giulia Casorati, Claudia Chiodoni, Paolo Della Bona, Olga Blazevits, Paolo Antonio Ascierto, Nicola Maurea, Valter Longo
Journal: Journal of Clinical Oncology (2024)

12029 Background: Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation as cancer therapeutics with the potential to increase survival. However, ICIs-induced side effects ranging from autoimmune endocrine disorders to mucositis and to a rare but clinically significant cardiotoxicity with high rate of mortality represent important limitations. Cardiovascular complications in ICIs-treated patients includes myocarditis, vasculitis, arrhythmia, fibrosis and heart failure. Moreover, both the limited efficacy in a large portion of patients and the acquisition of resistance represent additional limitations for ICIs, underlining the need for new immunotherapy strategies. Fasting mimicking diets (FMDs) applied for several days periodically are emerging as highly promising enhancers of a wide variety of cancer therapies including immunotherapy. Here, a preclinical study in melanoma-bearing mice treated with two combinatorial ICIs therapies (anti-OX-40/PDL-1 or antiCTLA-4/anti-PD-1) during a standard or FMD was performed. Methods: Melanoma or lung cancer-bearing mice ( C57BL/6J female mice, 6–8 weeks old) were treated with two combinatorial ICIs therapies (anti-OX-40/PDL-1 or antiCTLA-4/anti-PD-1) during a standard diet or FMD for 21 days. Tumors were measured every 3–4 days using a digital caliper. Mice were monitored for tumor growth and survival. Mice were killed when tumor volume reached 1.5 cm3. Flow cytometry analysis of tumor-infiltrating lymphocytes and apoptosis, collagen quantification in myocardial tissues, quantification of CD3+ and CD8+ cells in myocardial tissues, of plasma and myocardial cytokines, and several pro-inflammatory biomarkers were performed through selective ELISA methods and western blotting analysis. Results: FMD cycles in combination with anti-OX40/anti-PD-L1 also show a trend for increased effects against a lung cancer model. As importantly, the cardiac fibrosis, necrosis and hypertrophy caused by immune checkpoint inhibitors are prevented/reversed by FMD treatment in both cancer models whereas immune infiltration of CD3 + and CD8 + cells in myocardial tissues and systemic and myocardial markers of oxidative stress and inflammation are reduced. These results indicate that FMD cycles in combination with immunotherapy can delay cancer growth while reducing side effects including cardiotoxicity. Conclusions: This study sets the stage for clinical trials aimed at assessing the ability of FMD to increase the efficacy of immunotherapy while reducing its side effects. These results also indicate that the anti-inflammatory and protective effects of FMD cycles in combination with ICI could affect other organs and systems.
Cardiac and mortality outcomes in patients with breast cancer undergoing trastuzumab-based therapies.
Authors: Max Puthenpura, Heya Batah, Hardik Patel, Lorenzo Braghieri, Arianne Clare Agdamag, Diego Sadler, Halle C. F. Moore, Rohit Moudgil
Journal: Journal of Clinical Oncology (2024)

12027 Background: Trastuzumab is a cornerstone treatment for HER2-positive breast cancer. It is traditionally associated with adverse cardiac outcomes. However, the role of multi-line trastuzumab therapy on cardiac outcomes remains unknown. We examined the cardiac and mortality outcomes of multi-line trastuzumab therapies compared to single-line treatments. Methods: This is a single-center retrospective study of 275 adult patients from 2010 – 2017 who completed at least one course of trastuzumab-based therapy without interruption for toxicity. This included any breast cancer stage or type with longitudinal data available for comparison. The primary endpoint was Major Adverse Cardiovascular Events (MACE) defined as non-fatal stroke, non-fatal myocardial infarction (MI), acute heart failure (AHF) admission, and AHF readmission within 5 years of starting treatment. All-cause mortality was collected with cardiac death specified. Cox regression analysis compared cardiac and all-cause mortality at 1, 3, and 5 years from starting treatment. Logistical regression was used to analyze MACE outcomes within 5 years. Results: Patients were all female, averaged 56.7 years old when starting treatment, and 96% Caucasian. 220 patients had only one line of trastuzumab-based therapy while 55 had at least two lines of treatment. The two groups had no significant difference at 1 year for all-cause mortality. However, multi-line therapies were associated with a higher likelihood of all-cause mortality within 3 years (Hazard Ratio (HR) 5.0 [1.8-14.0]; p = 0.002) and 5 years (HR 3.8 [1.2–8.7]; p = 0.002) when compared to single-line therapy. For the single-line therapy patients, 58.3% of deaths were cancer-related at 3 years from starting treatment, and 61.5% as of 5 years. Multi-line therapy patients demonstrated 100% cancer-related death at both 3 and 5 years from starting treatment. Multi-line therapies were also independently associated with higher MACE outcomes within 5 years compared to single-line therapy (Odds Ratio 5.2 [1.5-17.9]; p = 0.009). Of the single-line therapy population, 0.5% had a non-fatal stroke, 0.5% had a non-fatal MI, 2.7% an AHF admission, and 1.4% an AHF readmission. Of the multi-line therapy patients, 7.2% had non-fatal strokes, 1.8% a non-fatal MI, 3.6% an AHF admission, and they had no AHF readmissions. There was no significant difference in cardiac mortality at any point. Conclusions: Multi-line trastuzumab therapy in breast cancer is associated with higher all-cause mortality after 1 year from starting treatment. Most importantly, multi-line therapies were identified as an independent risk factor for MACE, particularly heart failure and stroke, within 5 years. Therefore, survivors should be closely monitored for cardiac events after the first year of starting treatment and identified for early stroke prevention strategies.
Impact of protein-energy malnutrition on patients with breast cancer hospitalized for acute decompensated heart failure: Insight from the NIS database 2020.
Authors: Elvis Obomanu, Phuuwadith Wattanachayakul, Colton Jones, Yajur Arya, Arshi Syal, Karecia Byfield, Sarah Eidbo, Akshay Ratnani, Sakditad Saowapa, Natchaya Polpichai, Chalothorn Wannaphut, Carlo Casipit, Bruce Adrian Casipit, Ryan Mayo
Journal: Journal of Clinical Oncology (2024)

12030 Background: The breast cancer patient is at risk of acute decompensated heart failure (ADHF) and protein-energy malnutrition (PEM) either from the effects of chemoradiation or primary cancer. There have been several studies on patients with breast cancer and ADHF. However, the exact impact of concurrent PEM on patients with breast cancer admitted for ADHF is unclear. We aim to assess how PEM impacts breast cancer patients admitted with ADHF. Methods: We examined the 2020 US National Inpatient Sample (NIS) to explore how concurrent PEM affects breast cancer patients admitted for ADHF. Participants aged 18 and older were identified using relevant ICD-10 CM codes. A survey multivariate logistic and linear regression analysis was used to calculate the odds ratio (OR) for the outcomes of interest. Results: We identified 30,555 breast cancer patients with ADHF, with a mean age of 77±10 years; 99% were female. Caucasian accounted for 71.4%, followed by Black (17.5%), Mexican American (5%), and Asian (3%). Of these, 6.07% (1854/30,555) had a concurrent PEM diagnosis. In a survey multivariable regression model adjusting for patient and hospital factors, comorbid PEM was significantly associated with prolonged length of stay (β 2.09, 95% CI: 1.68–2.49, P &lt;0.001), increased risk of in-hospital mortality (aOR 2.61, 95% CI: 1.60–4.29, P &lt;0.001), increased risk of cardiogenic shock (aOR 3.17, 95% CI: 1.78–2.59, P&lt; 0.001), anemia (aOR 1.43, 95% CI: 1.14 to 1.80, p 0.002), and total hospital charge $28,285 (95% CI: $21,743–34,827, P&lt; 0.001). Adverse events such as respiratory failure (aOR 1.17, 95% CI 0.91 to 1.50, p 0.212) and DVT (aOR 1.15, 95% CI 0.40 to 3.31, p 0.802) were observed but did not reach statistical significance. Conclusions: Our study demonstrated that comorbid PEM among hospitalized breast cancer patients for ADHF is associated with increased risks of in-hospital mortality, anemia, cardiogenic shock, prolonged length of hospital stays, and total hospital charges. The study also highlights that nutritional status may be a useful prognostic marker in breast cancer patients who are at risk for various cardiovascular morbidities associated with cancer treatment and the primary disease. Additional longitudinal cohort studies are required to improve the understanding of this association.
Predictive factors for cardiac events following concurrent chemotherapy and radiation with durvalumab consolidation for unresectable non-metastatic non-small cell lung cancer.
Authors: Nikita Pankaj Patel, Danielle Dressler, Mengou Zhu, Yingzhe Liu, Zequn Sun, Jyoti D. Patel
Journal: Journal of Clinical Oncology (2024)

12033 Background: The PACIFIC trial was a randomized phase 3 study which evaluated the use of Durvalumab as consolidation therapy after definitive chemoradiation for patients with unresectable non-metastatic NSCLC. There was a significant improvement in progression free survival and overall survival. It was established as a standard approach for management. Due to nonspecific activation of the immune system, immune related adverse events are commonly associated with ICIs. Immune related cardiotoxicity is less common however may present as arrhythmia, pericarditis, valvular disease, cardiomyopathy, and there is more recent data to suggest an acceleration of atherosclerotic plaque burden likely due to inflammation that can result from immune activation. In this population, there are usually several other risk factors for cardiac disease including age, history of tobacco use, exposure to cardiotoxic chemotherapy and chest radiation. The objective of this study is to quantify, characterize, and identify potential risk factors for cardiac events (CEs) that occur after exposure to concurrent chemotherapy and radiation followed by Durvalumab in patients with unresectable non-metastatic NSCLC. Methods: Patients who received concurrent chemotherapy and radiation followed by Durvalumab for treatment of NSCLC at a large academic medical center between January 1, 2017 and April 1, 2021 were retrospectively identified. Demographics, treatment history, cardiovascular comorbidities (pre-existing arrhythmia, coronary artery disease, diabetes mellitus, heart failure, hypertension, hyperlipidemia, cerebral vascular accident, peripheral artery disease, tobacco use) and CEs occurring within 5 years of treatment were collected by chart review. Logistic regression analysis was used to identify potential risk factors for cardiac events in this patient population. Results: Among 115 patients, 29 (25%) experienced CEs including 15 new/worsening arrhythmia, 11 new/worsening cardiomyopathy, and 9 new/worsening coronary artery disease. There were no cardiac deaths identified. The most common arrhythmia was atrial fibrillation. Pre-existing arrhythmia, dyslipidemia, and number of pack years showed significant association with cardiac events (p&lt;0.05). Cumulative dose of radiation was found to be marginally significant on logistic regression analysis (p=0.07). Patients on a statin had a slightly lower odds of cardiac event (OR 0.03, p=0.02). Conclusions: Cardiac events following exposure to concurrent chemotherapy and Durvalumab may occur in up to 25% of patients with unresectable non-metastatic NSCLC. Further retrospective analysis of changes in coronary atherosclerotic plaque burden across PET-CT with ICI exposure and correlation with cardiac events is underway.
Exploring the prevalence and disparities of heart failure in patients with lung cancer and the associated risk factor analysis.
Authors: Julia Vinagolu-Baur, Saad Javaid, Kelly Frasier, Vivian Li, Nataly Ortega Yaguachi, Evadne Rodriguez, Olivia Del Castillo, Raquel Batista, Kenlee Jonas, Laura Palma
Journal: Journal of Clinical Oncology (2024)

12028 Background: Lung cancer is the leading cause of cancer-related death in the United States. Previous studies have suggested that patients with lung cancers are at increased risk of cardiovascular comorbidities that increase the risk of death in these patients. We studied the disparities in the prevalence of heart failure and risk factor analysis in lung cancer patients. Methods: We utilized the National Inpatient sample (2019-2020) to identify the patients who were admitted with a primary diagnosis of lung cancer (local/regional + advanced metastatic disease) and had a concurrent diagnosis of Heart Failure (HF). Baseline demographic characteristics were analyzed to determine the disparities in the prevalence of HF in lung cancer patients. Multivariate logistic regression analysis was done to assess the association of heart failure with lung cancer. Results: A total of 221320 patients had lung cancer, and 25495 had concurrent HF. The mean age of patients with and without HF was 73 and 68, respectively, p&lt;0.001. HF patients had a greater percentage of males than females (55% vs 44%, P&lt;0.001). Female patients were less likely to have HF (OR=0.82(0.77-0.88), p&lt;0.001), and older age was associated with increased risk of HF in lung cancer patients (46-64 years, OR=8.23(1.13-59.49), p=0.03, &gt;65 years OR=15.08(2.07-109), p=0.007). In Lung cancer patients hyperlipidemia had the greatest risk of association with HF (OR=1.85(1.71-1.99), p&lt;0.001), followed by obesity (OR=1.78(1.60-1.99), p&lt;0.001), Diabetes (OR=1.70(1.56-1.85), p&lt;0.001), End stage renal disease (OR=1.61(1.25-2.06), p&lt;0.001) and COPD(OR=1.45(1.34-1.56), p&lt;0.001). Hypertension was associated with decreased odds of HF (OR=0.01(0.01-0.015), p&lt;0.001). Compared to the white population, the Black race had increased odds of association with HF (OR=1.40(1.25-1.56), p&lt;0.001). Compared to Medicare, patients with Medicaid and private insurance were less likely to have HF (OR 0.76(0.65-0.89), p=0.001; OR=0.59(0.52-0.66), p&lt;0.001, respectively). Patients in high-income groups had decreased likelihood of concurrent HF ($65,000-$85,999, OR=0.88(0.80-0.98), p=0.02 and &gt;$86,000, OR=0.88(0.78-0.99), p=0.04). Conclusions: Lung cancer patients of Black race, older age, and those with medicare insurance are at a higher risk of developing heart failure. The presence of hyperlipidemia, obesity, diabetes, end-stage renal disease, and COPD is considered to be among the most significant risk factors for the development of heart failure in lung cancer patients. Addressing underlying risk factors can enhance patient outcomes and promote overall quality of life in patients with lung cancer.
The CT-based multi-omics model for prognostic prediction and tumor microenvironmental alterations in retroperitoneal liposarcoma: A retrospective multicohort analysis.
Authors: Peidang Fan, Ping Tao, Zhenyu Wang, Jiongyuan Wang, Long Jiu Zhang, Yong Ying Hou, Liang Hong, Lijie Ma, Yong Zhang, Hanxing Tong
Journal: Journal of Clinical Oncology (2024)

11564 Background: Retroperitoneal liposarcomas (RPLS) are tumours with a poor prognosis. Due to the tumour heterogeneity of RPLS, no effective prognostic index has been established. Radiomics has the potential to non-invasively characterize the so-called radiological phenotype of RPLS. We aimed to develop and independently validate a CT-based multi-omics model for predicting prognosis and tumour microenvironment (TIME) in RPLS to guide neoadjuvant therapy in clinical application. Methods: In this retrospective multicohort study, we used five independent cohorts of RPLS patients at our centre (n = 173, Zhongshan hospital, Fudan University, China), and the external validation cohort comprising RPLS patients from another medical centre (n = 184, Shanghai Public Health Clinical Center, Fudan University, China), to develop and validate a CT-based multi-omics model predictive of neoadjuvant chemotherapy (n = 10) and radiotherapy (n = 20) response by combining contrast-enhanced CT images and RNA-seq genomic data (n = 59) from tumour samples to assess the immune and metabolic landscape. Using the training dataset, a CT-based radiomics workflow was developed, including manual delineation, sub-segmentation, feature extraction, and predictive model building by LASSO, which was validated according to the area under the curve (AUC) for the internal validation set and external validation set. The clinical-radiomic model was developed through Univariate and Multivariate Cox regression analysis. Kaplan-Meier and log-rank tests were used for the survival analysis. Results: A total of 436 patients recruited between September 2009 and October 2021 were included in the training, internal validation, and external validation sets. The OS-related CT-based radiomics models in the training, internal validation, and external validation sets predicted the AUC values of postoperative 5-year OS as 0.71, 0.85, and 0.82, respectively. Strikingly, the clinical-CT radiomics model showed superior prognostic ability in predicting postoperative 5-year OS of 0.83, 0.85, and 0.86. Furthermore, the clinical-CT radiomics risk score was significantly decreased in post-neoadjuvant chemotherapy and radiotherapy with more tertiary lymphoid structures (TLS) and immune cell infiltration, such as plasma cells and B cells, compared to pretreatment. KEGG and ssGSEA analysis further indicated that retinol metabolism was most significantly inhibited in the high clinical-CT radiomics risk score group. Conclusions: Our validated clinical-CT radiomics model can predict the prognosis and TIME of RPLS with excellent performance. This may be a promising way to improve prognosis prediction and risk stratification of patients treated with neoadjuvant therapy, when validated by further prospective randomised trials.
Anlotinib versus placebo as adjuvant therapy for completely resected high-grade soft tissue sarcomas: Interim results of a phase 2, double-blinded, randomized controlled trial.
Authors: Chun-Meng Wang, Xianglin Hu, Ling-ge Yang, Yu Xu, Wen-Ding Huang, Jian-rong Zhang, Zheng-Wang Sun, Mo Chen, Bi-qiang Zheng, Sheng-jian Zhang, Lin Yu, Tomohiro Fujiwara, Yong Chen, Yang-bai Sun, Matthew T. Houdek, Wangjun Yan
Journal: Journal of Clinical Oncology (2024)

11562 Background: High-grade soft tissue sarcomas (STS) pose a therapeutic challenge due to the high risk of recurrence, even following complete resection. Anlotinib is a multi-targeted tyrosine kinase inhibitor blocking angiogenesis pathways of VEGFR, FGFR, and PDGFR. Given a promising efficacy for treating patients with unresectable advanced STS in previous trials, we evaluated the role of anlotinib as adjuvant therapy for completely resected high-grade STS. Methods: In a single-center, double-blinded, randomized, controlled trial, eligible patients were those adults who had not received adjuvant chemotherapy regimens after complete resection of high-grade STS. Patients were randomly assigned in a 1:1 ratio to receive either oral 12 mg anlotinib or placebo once daily on days 1-14 every 3 weeks as a cycle, with up to six cycles until disease recurrence, unmanageable toxicity or death. The primary endpoints included 1-year, 2-year disease-free survival (DFS). Results: Between June 2019 and November 2023, 88 patients were randomly assigned to receive anlotinib (n=44) or placebo (n=44). With a median follow-up of 25.99 months at data accrual cutoff on Jan 15, 2024, the 1-year and 2-year DFS rates were 88% and 77% in the anlotinib group, compared to 64% and 58% in the placebo group. Compared to patients in the placebo group, patients in the anlotinib group had a reduced risk of disease recurrence (HR 0.47 [95% CI 0.22~1.00, P= 0.0445]). The median DFS was not reached. Based on tumor histology, the greatest improvement in DFS with anlotinib versus placebo was observed in patients with myxofibrosarcoma (1-year DFS rate: 82% versus 61%; 2-year DFS rate: 64% versus 43%, HR 0.54 [95% CI 0.17~1.65], P= 0.2698) and undifferentiated pleomorphic sarcoma (1-year DFS rate: 86% versus 67%; 2-year DFS rate: 78% versus 67%, HR 0.58 [95% CI 0.12~2.87], P= 0.4971). Thirty-eight patients experienced adverse events (AEs; 34 with grade 1~2, 4 with grade 3): 28 patients (64%) in the anlotinib group versus 10 patients (23%) in the placebo group ( P&lt;0.001). Three patients discontinued anlotinib, including two for proteinuria/hematuresis (2/44, 5%) and one for secondary poor surgical wound healing (1/44, 2%). Conclusions: Current results suggest anlotinib could lower disease recurrence risk in patients with completely resected high-grade STS, with an acceptable toxicity profile. Clinical trial information: NCT03951571 . [Table: see text]