bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiomics of MRI scans enables differentiation of benign from malignant soft tissue sarcoma.
Authors: Li Lin , Kaon William , Viswanathan Vidya Sankar , Kosaraju Vijaya K , Kosmas Christos , Devita Robert , Abboud Salim , Madabhushi Anant , Mangla Ankit 
Published: June 2022

11565 Background: Accounting for >15,000 cases annually, soft tissue sarcomas (STSs) represent a large spectrum of tumors with varying histology and clinical course. However, diagnosis of STSs on MRI is challenging due to its heterogeneous imaging phenotypes, such as surrounding soft tissue edema, vascular lesion characteristics, and specific imaging signs, such as splitting of fat between muscles. The goal of this study was to evaluate the utility of radiomic feature analysis for characterizing subtle heterogeneity patterns on T2-weighted MRI to distinguish benign and malignant STSs. Methods: T2-weighted MRI of N = 176 patients with STS were retrospectively obtained from a single institution. (Table) Tumor regions were manually annotated by a radiologist. The radiomic features included textural features, e.g. gray-level co-occurrence matrix features, which quantify the correlation between textural patterns within annotated regions. Maximum relevance minimum redundancy feature selection was employed to identify top 10 radiomic features that are associated with STS malignancy. Then, the identified features were integrated to generate a radiomic risk score (RRS) via logistic regression on a 10-fold cross validation to differentiate benign and malignant STS. Multivariate analysis and the area under the receiver operating characteristic curve (AUC) were employed to evaluate the association of RRS and clinical parameters, including age, gender, and STS location, with STS malignancy. Results: Multivariate analysis illustrated that age and RRS are independent variables in predicting STS malignancy (p < 0.05). The RRS yielded AUC as 0.76 (confidence interval (CI): 0.69-0.83), age 0.71 (CI: 0.64-0.79) and the combination of the RRS and age 0.84 (CI: 0.78-0.90). Conclusions: The RRS generated by radiomic features was found to be a significant predictor of STS malignancy. Furthermore, RRS could provide complementary information to the clinical parameters in differentiating benign and malignant STSs.[Table: see text]
Genetic abnormalities and aberrant expression of genes involved in chromosome segregation and mitosis in patients with chromosomally unstable malignant soft tissue tumors haboring extensive somatic loss-of-heterozygosity (LOH).
Authors: Takahashi Katsuhito , Miyaji Yasutomo , Higuchi Hajime , Komohara Yoshihiro , Aida Shinsuke , Yashima Jun , Yamamoto Hiromasa , Suzawa Ken , Takahashi Yuko , Toyooka Shinichi , Narahara Hiroyuki , Yotsumoto Junko , Oyama Yu , Ono Yasuo , Teraoka Satoshi 
Published: June 2022

11576 Background: Malignant soft tissue tumor is a rare cancer with few therapeutic options. Recent genomic analysis of soft tissue sarcoma (STS) revealed a high degree of chromosomal instability (CIN) including genome-wide copy number alteration, aneuploidy, whole genome doubling and chromothripsis. In STS patients, we observed extensive somatic LOH, a hallmark of CIN, which is haploid of germline mutations/variants in cancer-related genes. CIN of STS genome implicates abnormalities in chromosome segregation and mitosis. So far, studies on this issue, however, have not been reported in STS patients. Methods: We recruited 155 patients with metastatic/recurrent malignant soft tissue tumors (135 female and 20 male, mean age 51 at analysis, 100 LMS, 19 LPS, 4 ESS, 3 UPS, 3 AS, 3 MPT, 3 GIST and others) with information of familial cancer burden. Whole exome sequencing and analysis were performed in both blood and tumor samples as described in 2018ASCO. KIF18A expression was assessed by immunohistochemistry. Results: Patients with tumors harboring less than 33% somatic LOH in a total of somatic and LOH mutations/variants in 595 COSMIC genes (n = 54) have a better prognosis than those (34-66%, n = 49, 67-100%, n = 52) with tumors harboring more LOH genes (5-year OS; 71% vs 52% or 46%, p = 0.0299, p = 0.0117, respectively). Neither TMB nor MSI status was associated with LOH. Of the genes involved in chromosome segregation and mitosis, we found that a family of ARHGAP genes which play a role in the spindle assembly and Aurora A kinase activation was frequently mutated in both tumor and germline genomes (n = 81 in a total of 155). Damaging ARHGAP mutations/variants in tumors are correlated with higher LOH values (54±3.4%, n = 81 vs. 39±3.3%, n = 74. mean±SE, p = 0.0021) and poor prognosis of patients (5-year OS; 58% n = 81 vs. 41% n = 74, p = 0.0098). We also found that elevated and robust expression of a mitotic kinesin KIF18A in tumors harboring higher LOH and/or damaging ARHGAP mutations/variants (n = 12) but not in lower LOH tumors without ARHGAP mutations/variants (n = 4). Conclusions: This study, for the first time, demonstrates that genetic abnormalities and aberrant expression of genes involved in chromosome segregation and mitosis in patients with malignant soft tissue tumors. The results reveal a novel target of drug discovery for incurable STS because CIN tumor cells are shown to be particularly vulnerable to KIF18A inhibition, while somatic, diploid cells are not.
Impact of acetaminophen on the efficacy of immunotherapy in patients with cancer.
Authors: Bessede Alban , Marabelle Aurelien , Guegan Jean-Philippe , Peyraud Florent , Danlos François-Xavier , Cousin Sophie , Chaput Nathalie , Spalato Mariella , Roubaud Guilhem , Cabart Mathilde , Khettab Mohamed , Chaibi Assia , Rey Christophe , Nafia Imane , Mahon François-Xavier , Soria Jean-Charles , Italiano Antoine 
Published: June 2022

12000 Background: Pain is the most common symptom experienced by patients with advanced cancer. Acetaminophen (APAP, commonly known as paracetamol) alone or in combination with a weak opioid, such as codeine or tramadol, is usually considered as the first-line strategy to manage mild-to-moderate pain in this setting. Although generally considered to be safe, several evidences suggest that APAP may have negative immunomodulatory effects. Randomized studies have shown that APAP use is associated with blunted vaccine immune responses. Given its potential to impair vaccine effectiveness, the World Health Organization stated in 2015 that administration of APAP before or at the time of vaccination is not recommended. This study aimed to assess APAP impact on efficacy of immunotherapy in patients with cancer. Methods: Exposure to APAP was assessed by plasma analysis and was correlated with clinical outcome in three independent cohorts of patients with advanced cancer who were treated with immune checkpoint blockers (ICB): the CheckMate 025 trial, n = 297 (NCT01668784, sponsor: Bristol Myers Squibb), the institutional biomarker program BIP n = 34 (NCT02534649, sponsor: Institut Bergonié, Bordeaux, France) and the institutional biomarker program PREMIS n = 297 (NCT03984318, sponsor: Gustave Roussy, Villejuif, France). APAP immunomodulatory effects were evaluated on a pre-clinical tumor model (MC38) and on human peripheral blood mononuclear cells (PBMCs) from healthy donors. Results: Detectable plasma APAP levels at treatment onset was associated with a significantly worse clinical outcome in ICB-treated cancer patients (HR for progression-free survival : 1.43, 95% CI 1.07–1.91, p = 0.015; HR for overall survival: 1.78 95% CI 1.18–2.68, p = 0.006), independently of other prognostic factors (age, performance status, number of previous lines of treatment, tumor type, number of metastatic sites, presence of liver metastases, LDH levels). APAP significantly reduced ICB efficacy in the pre-clinical MC38 model, as well as the production of PD1 blockade-related interferon-γ secretion by human PBMCs. Moreover, reduction of ICB efficacy in vivo was associated with significantly increased tumor infiltration by regulatory T cells (Tregs). Administration of APAP over 24 h induced a significant expansion of peripheral Tregs in healthy individuals. In addition, interleukin-10, a crucial mediator of Treg-induced immune suppression, was significantly upregulated upon treatment with ICB in cancer patients taking APAP. Conclusions: This study provides strong pre-clinical and clinical evidence of the role of APAP as a potential suppressor of antitumor immunity. Hence, APAP should be used with caution in patients treated with ICB.
Death with dignity utilization among patients with thoracic, head, and neck cancer.
Authors: Uy Natalie F. , Rodriguez Cristina P. , Daum Courtney , Baker Kelsey K. , Singer Jonathan , Hnida James , Lavell Laura , Sofie Katie , Cruz Jourdan , Eaton Keith D. , Santana-Davila Rafael , Loggers Elizabeth Trice 
Published: June 2022

12032 Background: Death with Dignity (DWD) legislation, which took effect in 2009 in Washington state, allows terminally ill patients (pts) to self-administer physician-prescribed, life-ending medication. Thoracic, head and neck cancer (THN) pts are among the top cancer types requesting DWD; however, data describing this group are limited. Methods: This retrospective chart review, conducted at Seattle Cancer Care Alliance/University of Washington and Fred Hutch, collected demographics, disease, treatment, support services and steps of the DWD process. We tested the association between disease characteristics of interest and DWD completion using Fisher’s Exact test. Results: Between Jan 2014 and October 2020, 498 pts inquired about DWD, and 108 (22%) were THN pts. Among THN pts, 51 (47%) only initiated the DWD request process, 35 (33%) only completed the DWD request process, and 22 (20%) completed the DWD request and self-administered the medication. Pts were white (n=90, 83%), male (n=64, 59%), primarily English speaking (n=103, 95%), nonreligious (n=69, 64%), single/divorced/non-partnered (n=55, 51%), and insured (n=103, 95%). Median age at request was 68 years (range 35-88). The table details THN DWD utilization. At time of DWD request, the median time from diagnosis was 14 months (range=0.2-242.7), and 62 (57%) had received ≥2 lines of therapy. Among 78 (72%) pts who received systemic therapy, 51 (65%) were ≥30 days from last therapy to time of death. Within 30 days prior to DWD request, 30 (28%), 25 (23%), and 7 (7%) pts saw social work, palliative care, and spiritual health respectively, and 35 (32%) were hospice-enrolled. Stage IV at diagnosis had higher rates of DWD medication use (p=0.05). There was no significant correlation between DWD medication use and primary site, ECOG score at request, insurance type, mental health diagnosis, use of depression/anxiety or pain medications, or hospice enrollment during DWD process. Conclusions: THN pts requesting DWD were predominantly white, nonreligious, insured males. Pts with advanced stage at diagnosis were more likely to use DWD medication. There was a higher proportion of DWD medication use with poorer performance status, and no association between use of depression/anxiety, pain medications, or utilization of supportive care services and DWD medication usage. Future research should investigate DWD utilization among THN pts in multiple centers and states to evaluate these patterns. [Table: see text]
Cancer doesn’t know what day of the week it is: Temporal trends in day of death, 2000-2017.
Authors: Shah Kanan , Tao Anna , Chino Junzo P. , Chino Fumiko 
Published: June 2022

12033 Background: Improving end-of-life care is an opportunity to reduce trauma for both patients and caregivers. Studies support the existence of a psychosomatic phenomenon known as the “holiday effect,” allowing critically ill patients to enter a bargaining phase and postpone death until a given event. We hypothesized that there may be a temporal trend as patients with cancer attempt to delay death until the arrival of family on weekends or the passage of a holiday. Methods: All deaths due to malignant neoplasms (ICD C00-C97) from 2000-2017 were collected from the National Center for Health Statistics. Outcomes were the days of week and months of year that death occurred. Weekend mortality was defined as death on Friday, Saturday, or Sunday. Holiday mortality was defined as death in December or January. Chi-squared tests were performed to determine differences in deaths by day or month. Logistic regression examined associations between day or month of death and age, education, race/ethnicity, location of death, marital status, race, and sex. Statistical analyses were performed using SAS statistical software, version 9.4 (SAS Institute Inc). Results: 10,305,990 deaths due to cancer were recorded from 2000-2017. Deaths were not uniform across day of week or month of year (p < 0.001 each). Each year, rates of death increased progressively from Monday to Thursday, peaked on Friday and Saturday, and declined on Sunday. There was a relative 3.4% difference in death rate between the peak on Friday and nadir of deaths on Monday. Each year there was a consistent increase in deaths in December and January, with a nadir in February with a relative difference of 10.2%. Multivariate logistic regression assessed associations in weekend and holiday cancer death. Non-hospital death (home, nursing facility, hospice) was more likely to occur on the weekend (aOR from 1.03-1.05, p≤0.01 for all). Hispanic patients (aOR 1.01, p = 0.001) were more likely to die on weekends. Females (aOR 0.99, p = 0.02), those who were divorced (aOR 0.99, p = 0.04) and those with pancreatic cancer (aOR 0.99, p = 0.01) were less likely to die on weekends. Non-hospital death was less likely to occur on Holiday months (aOR from 0.95-0.96, p≤0.01 for all). Those > 75 were more likely to pass away in Holiday months compared to younger age groups (OR 1.02-1.03, p < 0.05 for both). Cancer type was associated with holiday mortality; those with breast or prostate cancer were more likely to pass away (OR 1.01, p < 0.05 for both) during the holidays compared to those with lung cancer. Conclusions: There is a human element to death. The unequal distributions of deaths due to cancer in this study are small but significant; they suggest a non-biological variation that precludes cancer mortality from being strictly date agnostic. Temporal trends in cancer death highlight an opportunity to improve end of life care and demonstrate how care should shift focus to what matters to patients including time with family.
Sociodemographic factors associated with end-of-life palliative care utilization in female breast cancer: A national inpatient database analysis.
Authors: Hsieh Tien-Chan , Wang Yuyao , Zou Guangchen , Zheng Jiayi , Kloss Robert A. 
Published: June 2022

12035 Background: Palliative care (PC) has been shown to improve end-of-life quality in cancer patients. Nevertheless, several studies suggest that PC utilization is associated with socioeconomic factors. Patients with breast cancer, the most common neoplasm in women in the U.S., has lower PC utilization than those with other malignancies. We aim to investigate any sociodemographic barriers that are associated with the inpatient PC utilization in female breast cancer in the U.S. at the end of life. Methods: We used the National Inpatient Sample database of Healthcare Cost and Utilization Project, an all-payer inpatient care database in the United States, with data years 2014-2019. The end-of-life case was defined as hospitalized at least three days and passed away. We included all adult women (age at least 18 years old and female gender in electronic health records). The breast cancer cases were identified with International Classification of Diseases (ICD) 9th or 10th edition within the top three diagnoses. PC consultation could be identified with the ICD procedure code. Comorbidities were controlled with Charlson Comorbidity Index. After univariable analysis, the factors that were statistically associated with PC utilization would subsequently be added to the multivariable logistic regression model. Results: Between the year 2014 to 2019, we identified a total of 2,226 adult female patients who had breast cancer as their top three diagnoses and were hospitalized at least three days before death. 217 (9.7%) cases were 40-49 years old; 441 (19.8%) cases were 50-59 years old; and 1,455 (65.4%) patients were at least age 60 or above. The top three racial groups were Caucasian 1,420 (63.8%), African American 418 (18.8%), and Hispanic 166 (7.5%). 1,267 (56.9%) of all the cases had PC consult. African American (adjusted odds ratio [aOR]: 0.75; p < 0.005) and Hispanic (aOR: 0.62; p < 0.05) were significantly associated with less PC utilization than the Caucasian reference group in multivariable regression model. Lower PC prevalence was also observed at rural hospitals and Midwest region. Higher income group and private insurance no longer showed statistically significant higher PC utilization after adjusted for other variables. Conclusions: In end-of-life hospitalization with breast cancer as primary diagnosis, racial and hospital resource factors were significantly associated with the PC utilization. Cultural difference could be associated with the lower PC prevalence since adjusting income and insurance types could not explain the disparities in PC utilization among different racial groups. Future study should investigate and address the disparities of PC utilization in female terminal breast cancer.
The impact of diabetes on the performance of skeletal muscle density (SMD) in screening for frailty: Findings from the Cancer and Aging Resilience Evaluation (CARE) Registry.
Authors: Thai Sydney T , Lund Jennifer Leigh , Poole Charles , Sturmer Til , Harmon Christian , Al-Obaidi Mustafa , Williams Grant Richard 
Published: June 2022

12037 Background: SMD is a marker of myosteatosis that can be obtained from routine computed tomography (CT) imaging and could be used to screen patients for further frailty evaluation. But diabetes (DM) is linked with myosteatosis in men and SMD utility for patients with DM is unknown. We assessed SMD performance as a frailty screening tool in older adults with primarily gastrointestinal cancer and compared performance in patients stratified by sex and DM. Methods: We analyzed CARE Registry patients at baseline, a sample with mostly late-stage, gastrointestinal malignancies. Frailty and DM were captured in the CARE tool, a patient-reported geriatric assessment. SMD was calculated from CT scans at L3 vertebrae. Analyses were run for each sex and by DM status. We used linear regression to assess crude associations of SMD and frailty score. SMD performance in classifying frail status (vs. non-frail) was analyzed with 1) area under the receiver operating characteristic curves (AUC) and confidence intervals (CIs); and 2) sensitivity and specificity for sex-specific SMD quartile cut-offs (Q1, median, Q3). Cut-off performance was compared between patients with DM vs. without using differences in sensitivity and specificity and CIs. CIs were estimated with 2,000 bootstrap replicates. Results: The analytic sample (N=874; 27% DM, 32% frail) was 39% female with median age 68 years. For each sex-DM subset, regression results had negative slopes indicating that low SMD was associated with higher frailty score. AUCs for women with and without DM were 0.57 (95% CI 0.45-0.69) and 0.62 (0.54-0.70). AUCs for men with and without DM were 0.68 (0.59-0.77) and 0.58 (0.52-0.65). Sex-stratified sensitivity and specificity results are below. Median cut-offs had both sensitivity and specificity >0.50; Q3 cut-offs had higher sensitivity but low specificity. Conclusions: SMD could be used to pre-screen older adults with and without DM for further clinical frailty assessment. With high-sensitivity cut-offs (Q3), 13% to 26% of frail patients could be missed. Compared to other groups, SMD pre-screening for men with DM may miss the fewest frail patients but would produce many false-positives. [Table: see text]
Improved overall survival of metastatic cancers in the United States across all age groups in the immunotherapy era: Implications for considering elderly patients (age ≥ 75) for immune checkpoint inhibitors (ICIs).
Authors: Chen Yu-Wei , Tucker Matthew D , Yasin Hesham Abdallah , Guo Xingyi , Shu Xiao-Ou , Rini Brian I. 
Published: June 2022

12039 Background: ICIs have changed the treatment paradigm in many cancer histologies. Population-level data regarding the impact of ICIs on the contemporary US cancer patients is scarce. In addition, elderly patients were underrepresented in the landmark trials. Methods: Metastatic cancers (melanoma, lung cancer, kidney cancer, head and neck cancer, Hodgkin’s lymphoma, and urothelial cancer) diagnosed between 2004-2018 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The year of the first FDA approved ICI in each cancer site was considered the commencement of the ICI era. The impact of metastatic cancers diagnosed in the ICI era was assessed in each age group (<65, 65-75, and ≥75) using multivariable Cox regression after adjustment for age, sex, race, household income and residence status (metropolitan vs non-metropolitan) Results: There were 363,191 patients with metastatic cancers included in the analysis [lung cancer: 68%, head and neck cancer: 14%, Hodgkin Lymphoma: 7%, kidney cancer: 7%, urothelial cancer: 3%, and melanoma: 2%): 60% were male and 73% were non-Hispanic White. The median age was 66 (interquartile range: 57-75). After baseline adjustments for sociodemographic factors, metastatic cancers diagnosed in the ICI era had improved overall survival except urothelial cancer (Table). Results of overall survival and cancer-specific survival were consistent across all age groups (<65, 65-75, and ≥75). Among patients with age ≥75, metastatic cancers diagnosed in the ICI era had improved overall survival in melanoma (AHR: 0.81, p-value<.0001), lung cancer (AHR:0.91, p-value<.0001), kidney cancer (AHR: 0.89, p-value: 0.0004), head and neck cancer (AHR:0.82, p-value<.0001), Hodgkin lymphoma (AHR: 0.75, p-value:0.003) but not in urothelial cancer. Conclusions: Metastatic cancers diagnosed in the ICI era had improved overall survival and cancer-specific survival including the subgroup of age ≥ 75. ICIs should not be withheld in elderly patients solely due to chronological age. [Table: see text]