bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of long-term and short-term survivors of metastatic uterine leiomyosarcoma.
Authors: Sia Tiffany Y. , Brown David N , Miller Kathryn M , Leitao Mario M. , Abu-Rustum Nadeem , Chiang Sarah , Weigelt Britta , Hensley Martee Leigh 
Published: June 2024

11542 Background: While some metastatic uterine leiomyosarcomas (uLMS) are clinically aggressive, others have a more indolent disease pace, suggesting biologic heterogeneity. Our objective was to determine whether the molecular characteristics of metastatic uLMS tumors differed between long-term survivors (LS) and short-term survivors (SS). Methods: Patients with metastatic uLMS between 1/1/2000 – 11/31/2020 who received care at our institution and had tumor tissue available were included. uLMSs were subjected to a targeted DNA next-generation sequencing panel of up to 505 cancer-related genes. Metastatic overall survival (mOS) was calculated from the date of diagnosis of metastatic disease until the date of death or last follow-up. LS was defined as mOS >2 years and SS as mOS <2 years. Appropriate statistical tests were used. Results: Our cohort included 17 LS and 10 SS (Table). uLMSs from LS harbored TP53 alterations in 58% of cases compared to 90% of SS (P<0.001). Rate of RB1 alterations in LS was 76% compared to 50% in SS (P<0.001). Rates of somatic genetic alterations affecting ATRX(11% LS vs. 20% SS) and BRCA2(47% LS vs. 50% SS) were similar between groups (P>0.05 for both). Most BRCA2alterations (92%) were homozygous deletions. Levels of chromosomal instability as quantified by the fraction of genome altered was similar between groups (median 27.3% in LS versus 22.9% in SS, p=0.26). Tumor mutational burden was low in both groups. Conclusions: While uLMS from LS and SS have similar levels of chromosomal instability and tumor mutational burden, uLMS in LS have lower rates of TP53 alterations compared to SS patients, as well as compared to previously reported rates in uLMS. Rates of RB1alterations were higher in LS compared to SS. Interestingly, the rate of BRCA2alterations in both LS and SS is higher than previously reported and provides rationale for next-generation sequencing in patients with metastatic uLMS. Further studies in larger cohorts to validate these findings are warranted. [Table: see text]
Analysis of the time to progression in patients who underwent metastasectomy plus isolated lung chemoperfusion for disease recurrence after metastasectomy alone.
Authors: Levchenko Evgeny , Mikhnin Aleksandr , Senchik Konstantin , Mamontov Oleg , Ergnyan Stepan , Levchenko Nikita , Yurin Roman , Khandogin Nikolay , Nyukhlov Evgeny , Imyanitov Evgeny 
Published: June 2024

11568 Background: The combination of pulmonary metastasectomy (ME) with isolated lung chemoperfusion (ILuP) has shown promising results, however, a direct comparison of the clinical outcomes obtained by ME plus ILuP versus ME alone is complicated. The heterogeneity of patients in terms of cancer types, number of metastases and composition of prior systemic therapy adds to the difficulties of this analysis. Methods: Patients who initially received ME alone, and then ME plus normothermic ILuP after the disease relapse, were considered. The aim of the study was to compare the time to pulmonary disease progression (TTP) after the first and second interventions (TTP1 and TTP2, respectively) in the same subjects. Results: Of 225 patients who underwent ME plus ILuP in 2007 - 2020, we selected 48 patients who received this treatment due to pulmonary disease progression after ME alone. There were 16 patients with soft tissue sarcoma, 8 patients with osteosarcoma, 14 colorectal cancer cases and 10 patients with other tumor types. The mean number of metastases was 2.94 before ME alone and 4.33 before ME plus ILuP. Cisplatin was used in 30 patients at a mean dose of 191.8 mg, and melphalan was utilized in 18 subjects at a mean dose of 44.1 mg. The median follow-up was 31.1 months. The median TTP1 was 6.9 months, and the median TTP2 was 19.0 months (p <0.0001). TTP2/TTP1 ratio equal or above 1.5 was observed in 34 out of 48 patients (71%). Conclusions: This is the first study comparing the results of ILuP plus ME versus ME alone in the same patients. The data obtained strongly support the feasibility of adding isolated lung chemoperfusion to surgery in patients amenable to excision of lung metastases.
Walking dose required to achieve a clinically meaningful reduction in cancer-related fatigue among patients with breast cancer receiving chemotherapy: A URCC NCORP nationwide prospective cohort study.
Authors: Mattick Lindsey Jean , Lin Po-Ju , Mustian Karen Michelle , Peppone Luke Joseph , Gada Umang , Samuel Stephen Rajan , Clark Viktor , Yilmaz Sule , McGuire Jeremy , Conlin Alison Katherine , Weiselberg Lora Rose , Mitchell Jerry W. , Janelsins Michelle Christine 
Published: June 2024

12008 Background: Exercise is recommended by ASCO as a treatment for cancer-related fatigue (CRF) - one of the most pervasive toxicities patients with breast cancer experience. Current oncology guidelines recommend aerobic exercise (e.g., walking) at a weekly dose of 150 minutes of moderate intensity or 75 minutes of vigorous intensity. While these recommendations exist and are effective for treating CRF, patients with breast cancer struggle to achieve these levels of exercise, especially at a vigorous intensity during chemotherapy. The purpose of this study was to determine the doses of low and moderate intensity walking required to elicit a clinically meaningful reduction in CRF. Methods: As part of a nationwide prospective cohort study, 580 female breast cancer patients (stage I-IIIC; receiving chemotherapy) were recruited from 19 University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) Research Base locations. CRF (Multidimensional Fatigue Symptom Inventory) and exercise dose (i.e., walking via ACLS Physical Activity Measure) were measured at pre-chemotherapy, 1-month post-chemotherapy, and 6-months post-chemotherapy. Exercise dose was measured in METs (energy expenditure normalized for body weight and time; 1 MET = 1 kcal/kg/hr) and converted into walking time (minutes) and intensity (mph). A low-intensity walking pace is < 2.5mph (< 3 METs), and a moderate-intensity walking pace is 2.6-4.5mph (3.1-6 METs). Results: Pre-chemotherapy, patients with breast cancer averaged walking 40-60 minutes/week at a low intensity or 20-38 minutes/week at a moderate intensity (median: 2.0 MET hrs/wk). Linear mixed modeling demonstrated a higher amount of walking significantly predicts lower CRF at all three time points (β: -0.26, SE: 0.08; p < 0.001). Logistic regression identified that patients who increase their walking by 111-162 minutes at a low-intensity pace or 54-108 minutes at a moderate-intensity pace (i.e., 1 SD) are 43% more likely to experience a clinically meaningful reduction in CRF (- 4.5 MFSI total) from pre-chemotherapy to 1-month post-chemotherapy (SD: 5.4 MET hrs/wk; OR: 1.43, 95% CI: 1.19-1.72; p < 0.001). Conclusions: Over the course of chemotherapy, patients with breast cancer who can increase their walking at a low intensity pace (< 2.5 mph) up to 151-222 min/wk or at a moderate intensity pace (2.6-4.5 mph) up to 74-146 min/wk are 43% more likely to have clinically meaningful lower levels of CRF post-chemotherapy.
Effect of nurse-led multi-disciplinary treatment on patients with head and neck tumors: A randomized controlled trial.
Authors: Wang Jingjing , Cai Lei , Pei Yiyan , Li Juejin , Wei Zhigong , Li Ruidan , Su Yonglin , Hu Xiaolin , Peng Xingchen 
Published: June 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&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 .
Cardiac and mortality outcomes in patients with breast cancer undergoing trastuzumab-based therapies.
Authors: Puthenpura Max , Batah Heya , Patel Hardik , Braghieri Lorenzo , Agdamag Arianne Clare , Sadler Diego , Moore Halle C. F. , Moudgil Rohit 
Published: June 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.
Association between psychological distress and treatment efficacy in patients with newly diagnosed SCLC.
Authors: Wu Fang , Wang Shuxing , Zeng Yue , Peng Yurong , Liu Junqi , Tian Xinyu , Yao Shijiao , Liang Aoxi , Deng Chao , Qiu Zhenhua , Ma Fang , Liu Xianling , Hu Chunhong 
Published: June 2024

12107 Background: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy known for its rapid doubling time and high growth fraction. Despite advancements, treating SCLC remains challenging, necessitating improved strategies. Prior research indicates that psychological distress can impact cancer treatment efficacy, with severe psychological distress correlating with poorer prognosis. Our study delves into the psychological distress distribution among SCLC patients and identifies potential treatment targets. Methods: Patients newly diagnosed with SCLC, receiving either chemotherapy or immunotherapy as first-line treatment, were enrolled. Psychological distress, encompassing depression and anxiety symptoms, was assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales. Psychological distress hormone levels, including serum cortisol and adrenocorticotropic hormone (ACTH), were measured using ELISA kits before treatment initiation. Objective response rate (ORR) and median progression-free survival (PFS) were determined through chi-square tests, Kaplan-Meier analysis, and Cox regression methods. Results: A total of 97 patients diagnosed with SCLC were included in the study, with an average age of 61.5 years. Among them, 70 cases (72.1%) were classified as extensive stage, while 27 cases (27.8%) were limited stage. Psychological distress was present in 53 patients (54.0%). Patients experiencing psychological distress exhibited a significantly lower objective response rate (ORR) compared to those without distress (50.9% vs. 72.7%; P = 0.037), along with a shorter median progression-free survival (PFS) (8.40 vs. 19.47 months; 95% CI 7.84-12.96; P = 0.004). Furthermore, elevated serum cortisol levels (P < 0.001) were observed in patients with psychological distress. In addition, higher serum cortisol concentration (P = 0.011) was associated with a poorer response to chemotherapy and immunotherapy. Conclusions: Psychological distress is prevalent among patients with SCLC. Notably, those experiencing psychological distress tend to exhibit poorer responses to chemotherapy and immunotherapy. Our investigation has uncovered a potential mechanism involving neuroendocrine hormone resistance to treatment modalities. Clinical trial information: NCT05477979 .
Exploring the structure of psychological distress and its symptoms: A psychometric network analysis.
Authors: Rossi Alessandro , Marconi Maria , Mannarini Stefania , Calcaterra Andrea , De Cicco Luigi , Verusio Claudio , Di Lucca Giuseppe 
Published: June 2024

12112 Background: Psychological research is currently surging in oncological settings, with the construct of psychological distress gaining significant attention. Several studies have demonstrated that psychological distress can have profound adverse effects on adherence, therapy compliance, medical treatments, and overall quality of life (NCCN, 2015). However, it remains a challenging endeavor to attain a clear understanding of the implications of psychological distress in the daily lives of oncology patients. To address this gap, our study aimed to identify the central symptoms of psychological distress and elucidate their relationships. Methods: Oncological outpatients (N = 504; meanage = 67.15, SD = 10.16; 50% females) were recruited at the Presidio Ospedaliero of Saronno, ASST Valle Olona, Italy. The Psychological Distress Inventory-Revised (PDI-R; Rossi et al., 2022), utilized to measure internal, external, and general distress, demonstrated high internal consistency in assessing patients' psychological distress. As a preliminary step before conducting confirmatory factor analysis, we employed an analysis to assess the structural validity of the PDI-R. Subsequently, we performed a Psychometric Network Analysis with the EBICglasso algorithm (5000 bootstrap) to uncover the network structure of psychological distress and identify nodes with greater strength and expected influence. Results: The preliminary analysis indicated that the factorial structure demonstrates excellent fit indices [RMSEA = 0.055; CFI = 0.997; SRMR = 0.041]. Additionally, the Psychometric Network Analysis showed a high accuracy (CS-coefficient = 0.75). Psychological distress symptoms spontaneously clustered into internal and external distress, as per the model, with all symptoms showing noteworthy interconnections. Notably, the strongest connections were observed within the 'external distress' facet. On one hand, the Network Analysis revealed that item #7 (External distress: 'diminished interest in the world'; z = 1.480), item #2 (Internal distress: 'moments of dejection or depression'; z = 1.141), and item #8 (External distress: 'the illness has negatively influenced your relationships with others'; z = 0.542) were identified as nodes with both the highest strength and expected influence. Conclusions: These findings have meaningful implications for clinical practice, as clinical interventions should prioritize addressing symptoms that exhibit the strongest connections within the network. Given that these central nodes have the potential to influence all other connected symptoms, they represent crucial focal points for clinicians. Tailoring more targeted and efficient therapeutic approaches to address these central symptoms can have beneficial effects on medical treatments and enhance the overall quality of life for patients.
Correlation of baseline ENPP1 and cGAS expression in advanced solid tumors with intratumoral immune activation and clinical outcomes after treatment with the first-in-class oral ENPP1 inhibitor RBS2418, alone or in combination with pembrolizumab.
Authors: Marron Thomas Urban , Wainberg Zev A. , Spira Alexander I. , Gordon Michael S. , Chen Christopher , Segar Jennifer Margaret , Boccia Ralph V. , Berlin Jordan , Csiki Ildiko , Schanzer Juergen , Huang Ningwu , Glen Jeffrey , Klumpp Klaus , Misleh Jamal Ghazi 
Published: June 2024

2597 Background: ENPP1 is a nucleotide pyrophosphatase and phosphodiesterase. Its expression is associated with poor prognosis in cancer. ENPP1 inhibition protects cGAMP and ATP from hydrolysis and reduces adenosine levels in the TME, activates APCs and increases T-cell infiltration promoting anticancer immunity. RBS2418, a first-in-class, potent ENPP1 inhibitor, is evaluated as monotherapy and combination with pembrolizumab in advanced/metastatic solid tumors. Methods: Phase 1 dose escalation with 100, 200, 400 and 800 mg BID dose and selected expansion cohorts of RBS2418 alone or in combination with pembrolizumab (200 mg IV q3w) in patients who have failed all approved treatments including immunotherapy. Primary outcome measures are safety and PK. Tumor biopsy, and blood samples are collected to determine PK/PD and immune profiles using LC/MS, ENPP1 inhibition, immunofluorescence, IHC, flow cytometry, and TCR/RNAseq analysis. Results: All dose levels evaluated to date were safe and well tolerated with no DLTs. Median plasma concentrations of RBS2418 increased in a dose-dependent manner. Plasma and tumor concentrations of RBS2418 were above the ENPP1 inhibition EC90 level in all patients at all-time points tested. Preliminary analyses support the premise that ENPP1 and cGAS co-expression (EG+ phenotype) in tumors correlates with RBS2418 treatment associated immune activation and clinical benefit. Analysis of all currently available paired pre- and on-treatment biopsies showed on-treatment immune activation profiles in 100% (n=6) with EG+ phenotype and 0% (0/6) with EG- phenotype at baseline. Immune activation profiles include an increase in tumor-infiltrating T-cells and M2 to M1 macrophage switch, consistent with the mechanism of action. EG +/- phenotype and immune activation profile also correlated with observed clinical outcomes. Conclusions: Oral RBS2418 alone or with pembrolizumab has been safe, well tolerated with no DLTs at all dose levels evaluated to date in the ongoing Ph1 dose escalation and expansion study. The robust PK profile shows plasma levels enabling complete ENPP1 inhibition at all time points. Immune activation and observed clinical benefit of treatment in late line treatment of refractory metastatic solid tumors such as CRC and HCC was associated with baseline ENPP1 and cGAS protein expression in tumors. These results warrant further development of RBS2418 in advanced tumors and enrollment continues in expansion cohorts on this phase 1 study. Clinical trial information: NCT05270213 .