tbuckley/cabot-search huggingface dataset:
The association between the coronavirus disease 2019 (COVID-19) pandemic and quality of life and depression symptoms in patients with advanced lung cancer.
Authors: Lauren Heuer, Kathryn Elizabeth Post, Emily R. Gallagher, Chardria Trotter, Madeleine Elyze, Charu Vyas, Rachel Plotke, Joseph A. Greer, Jennifer S. Temel, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2021)

12122 Background: It is unclear whether patients with cancer experience greater distress as a result of the COVID-19 pandemic. Thus, we assessed the relationship of the COVID-19 pandemic with quality of life (QOL) and depression symptoms in patients newly diagnosed with advanced lung cancer. Methods: We conducted a cross-sectional study of patients with advanced lung cancer enrolled in two multisite randomized supportive care trials. We enrolled adult patients within 12 weeks of diagnosis of advanced lung cancer and an Eastern Cooperative Oncology Group (ECOG) Performance Status from 0 to 3 across 23 institutions in the United States. At the time of enrollment, participants completed the Functional Assessment of Cancer Therapy-Lung (FACT-L), which includes four wellbeing subscales (i.e., physical, social, emotional, and functional) as well as lung cancer symptoms, and the Patient Health Questionnaire-9 (PHQ-9) to assess their QOL and depression symptoms, respectively. We compared QOL and depression symptoms between participants enrolled prior to COVID-19 (i.e., those enrolled in the following time periods: March 2018 to January 2019 and March 2019 to January 2020) and during the COVID-19 pandemic (March 2020 to January 2021). We used linear regression models adjusting for age, race, gender, and time since diagnosis of advanced cancer to examine the relationship between the period of enrollment and patients’ QOL and depression symptoms. Results: A total of 860 patients were included in this analysis (665 participants enrolled prior to COVID-19 and 195 participants during COVID-19). The two cohorts did not differ significantly with respect to baseline demographic factors [Mean age 65.4 (SD = 11.4), 51.9% female]. In multivariate regression models, enrollment during COVID-19 was not associated with physical (B = -0.16, SE = 0.52, P = 0.763), social (B = -0.48, SE = 0.39, P = 0.217), emotional (B = -0.16, SE = 0.41, P = 0.693), functional (B = -0.83, SE = 0.55, P = 0.128) wellbeing, or lung cancer symptoms (B = -0.11, SE = 0.44, P = 0.806). Enrollment during COVID-19 was not associated with overall QOL (FACT-L: B = -1.32, SE = 1.69, P = 0.436) or depression symptoms (PHQ-9: B = -0.02, SE = 0.45, P = 0.973). Conclusions: Despite the prevailing belief that COVID-19 has negatively impacted QOL and distress in patients with cancer, we found no differences in QOL or depression symptoms in patients newly diagnosed with advanced lung cancer during the COVID-19 pandemic compared to those diagnosed prior to the pandemic. These findings suggest that factors other than the COVID-19 pandemic, such as patients’ experience with their cancer, contribute to their QOL and depression symptoms.
Phase II study of lenvatinib in combination with GEMOX chemotherapy for advanced intrahepatic cholangiocarcinoma.
Authors: Guo-Ming Shi, Zhou Jian, Jia Fan, Xiao-Yong Huang, Dong Wu, Fei Liang, Jia-Cheng Lu, Guo-Huan Yang, Yi Chen, Ning-Ling Ge, Yuan Ji, YY Hou, Hui-Chuan Sun, Shuang-Jian Qiu, Qing-Hai Ye, Xiao-Wu Huang, Ying-Hong Shi, Qiang Gao, Xin-Rong Yang, Zheng Wang
Journal: Journal of Clinical Oncology (2021)

e16163 Background: The prognosis of advanced intrahepatic cholangiocarcinoma (ICC) remains dismal with gemcitabine-based first-line chemotherapy. This study is to evaluate the safety and efficacy of lenvatinib in combination with gemcitabine and oxaliplatin (Gemox) chemotherapy in the advanced ICC. Methods: Locally advanced or metastatic ICC patients (pts) were given lenvatinib 12 mg/day (body weight ≥60 kg) or 8 mg/day (body weight &lt;60 kg) oral administration, once daily. They also received 1g/m² gemcitabine on Day 1 and Day 8, and 85 mg/m² oxaliplatin Q3W by IV for 6-8 cycles. The primary outcome was objective response rate (ORR) and secondary outcomes included safety, disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). ORR, DCR and PFS were measured according to RECIST 1.1. Treatment would be terminated by confirmed disease progression, unacceptable toxicity, or voluntary withdrawal. Results: From March 2020 to Sep. 2020, 30 pathologically-confirmed advanced ICC pts with a mean age of 59.2 (range, 33-74) years, including 14 women (46.7%), were enrolled at Zhongshan Hospital, Fudan University. At the end of last follow-up (February 10, 2021), the ORR was 30.0% (9/30; 95% CI: 14.7%-49.4%). The disease control rate (DCR) was 86.7% (26/30; 95% CI: 69.3%-96.2%). Median follow-up was 6.8 months. One pt with locally advanced disease was down-staged and then underwent resection. This patient remained disease-free survival at the end of last follow-up. 11 pts experienced disease progression and 8 pts have died. The median PFS and OS have not been reached. Median duration of response (DOR) has not been reached and responses were ongoing in 6/9 (66.7%) pts. 6-months OS rate was 92.6%. No grade 5 adverse event (AE) was observed in present study. 40.0% (12/30) of pts experienced grade 3 or higher AEs and 5 pts discontinued the treatment owing to fatigue (3 pts), jaundice (1 pt) and vomiting (1 pt). Conclusions: Addition of lenvatinib to Gemox chemotherapy provided modest efficacy with reasonable tolerability in advanced ICC patients. Clinical trial information: (NCT04361331). Clinical trial information: NCT04361331.
Efficacy and safety analysis of Chinese patients in monarchE: Abemaciclib combined with adjuvant endocrine therapy for high risk HR+, HER2- early breast cancer.
Authors: Shao Zhimin, Qingyuan Zhang, Chuan-gui Song, Quchang Ouyang, Zhenzhen Liu, Qiang Liu, Jifeng Feng, Joanne Wing Yan Chiu, Ling-Ming Tseng, Chenxi Qian
Journal: Journal of Clinical Oncology (2021)

522 Background: In monarchE, abemaciclib (oral CDK4&amp;6 inhibitor) plus endocrine therapy (ET) as adjuvant treatment for HR+, HER2- high risk early breast cancer (EBC), demonstrated a statistically significant improvement in invasive disease-free survival (IDFS) compared to ET alone. Here we present the efficacy and safety analysis of Chinese patients from monarchE. Methods: The overall study design was reported previously. Eligible patients were randomized to receive abemaciclib (150 mg BID for 2 years) combined with standard adjuvant ET or ET alone. The primary endpoint was IDFS per STEEP criteria. Secondary endpoints included distant relapse-free survival (DRFS), overall survival, and safety. Exploratory subgroup analyses were conducted among Chinese patients enrolled from Mainland China, Hong Kong, and Taiwan in the intent-to-treat (ITT) population. Results: A total of 501 Chinese patients were randomized to receive abemaciclib plus ET (259 patients) or ET alone (242 patients). At the time of data cutoff (July 8, 2020), 356 (71.1%) patients were still in the 2-year treatment period. A total of 26 IDFS events were observed (11 and 15 events in abemaciclib plus ET and ET arm, respectively). Comparing to ET alone, abemaciclib combined with ET reduced the risk of developing invasive disease or death by 34.3% (HR: 0.657, 95% CI: 0.301, 1.435) for Chinese patients, together with a clinically meaningful improvement in the 2-year IDFS rate (95.6% vs 92.1%). The addition of abemaciclib to ET also resulted in an improvement in DRFS (HR: 0.601, 95% CI: 0.245, 1.477) for Chinese patients, with the 2-year DRFS rate at 96.7% (ET alone: 93.4%). In the abemaciclib arm, the most frequent treatment-emergent adverse events (TEAEs) and grade ≥3 TEAEs: diarrhea (90.3% and 5.0%), leukopenia (76.8% and 21.2%), and neutropenia (76.4% and 23.9%), respectively. Conclusions: Abemaciclib combined with adjuvant ET demonstrated clinically meaningful IDFS and DRFS benefits among Chinese patients with HR+, HER2-, high risk EBC, which was consistent with the ITT population as reported previously. The safety profile of abemaciclib in Chinese EBC patients was consistent with global population and also with that observed in Chinese metastatic breast cancer patients. Clinical trial information: NCT03155997.
Different genomic profiling of sarcoma between Western and Chinese population.
Authors: Sheng Teng, Yun Yang, Jin Zhang, Xia You, Taiyan Guo, Qin Zhang, Qianqian Duan, Chuang Qi
Journal: Journal of Clinical Oncology (2021)

e23532 Background: Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. The clinical presentation and gene mutations in different subtypes are often atypical, and the profile of gene mutations vary widely. Meanwhile there are many genetic mutations difference between West countries patients and Chinese patients in many cancer types, however little is known about soft tissue tumors' difference. Methods: Next-generation sequencing data and clinical data were collected from 255 Western soft-tissue sarcoma patients (TCGA cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 271 Chinese soft-tissue sarcoma patients (Chinese cohort). Both somatic mutations and germline mutations were detected on the Chinese cohort, then we compared the somatic mutations between TCGA and Chinese cohort. Results: In Chinese cohort, top 5 mutant genes were TP53(35.69%), ATRX(14.12%), MUC16(12.94%), RB1(10.98%), CSMD1(8.24%); while in TCGA cohort were TP53(22.88%), MUC16(8.12%), RB1(6.27%), TERT(5.17%), NF1(4.80%). The mutation frequency of 7 genes were higher in TCGA cohort than in Chinese cohort: TP53(35.69% vs 22.88%, p = 0.0015), ATRX(14.12% vs 4.06%, p &lt; 0.001), CSMD1(8.24% vs 1.85%, p &lt; 0.001), LRP1B(6.27% vs 2.21%, p &lt; 0.05), CSMD3(3.92% vs 1.11%, p &lt; 0.05), EPHA7(3.92% vs 0.74%, p &lt; 0.05) and PIK3C2G(3.53% vs 0.37%, p = 0.009). However, TERT showed the opposite, which in TCGA cohort(1.57%) was lower than Chinese cohort(5.17%)(p &lt; 0.05). Meanwhile, we detected the germline mutations in Chinese cohort. There are three patients had BRCA1 mutations, the SLX4, TP53, MUTYH, ATM, ERCC3 and NBN were all only happened once. There were 21 patients from Chinese cohort had EWSR1-X fusions, including EWSR1-ERG(6/21, 28%), EWSR1-FLI1(6/21,28%), EWSR1-ATF1(4/21,19%), EWSR1-CREB1(1/21,5%), EWSR1-DCTN2 (1/21, 5%), EWSR1-POU5F1(1/21, 5%), EWSR1-WT1(1/21, 5%).Besides, we discovered a novel fusion gene EWSR1-DDIT3(1/21, 5%) in Chinese cohort. Conclusions: We described the general landscape and differences of genetic variation in Chinese and Western populations, we also discovered some new mutations such as novel fusion.In conclusion, comprehensive genomic profiling in a large cohort highlights the promise of targeted therapies.
Gene methylation and cytological atypia in random fine needle aspirates for assessment of breast cancer risk: 10-year follow up in average risk women.
Authors: Erica Wrubel, Mary Jo Fackler, Peng Huang, Natalie Pulliam, Amanda Montanari, Carola Maria Zalles, Saraswati Sukumar, Vered Stearns, Seema Ahsan Khan
Journal: Journal of Clinical Oncology (2021)

10520 Background: Alterations in DNA methylation occur early in tumorigenesis, and are a potential breast cancer risk biomarker. We previously reported a study where healthy volunteers underwent random fine needle aspiration (rFNA) of the breasts; cumulative methylation index of eight preselected tumor suppressor genes (CMI) was associated with the presence of cytological atypia in rFNA samples. We now report 10-year follow-up of this population, to evaluate whether increased CMI is associated with subsequent breast cancer development. Methods: 380 women, unselected by breast cancer risk, were enrolled. Demographics, breast cancer risk factors, lifetime Gail model risk estimates (Gail-LR), and %breast density were obtained at baseline. rFNA samples were assessed for cytopathology (Masood Score, MS) and CMI. Patients were contacted annually for 10 years to ascertain development of invasive or non-invasive breast cancer. In univariate analysis, log-rank test was used to compare breast cancer incidence rates between individuals with high and low baseline measures (separated by median). Area under the ROC curve was used to evaluate the cancer prediction accuracy. In multivariate analysis, the effect of CMI (after log-transformation to reduce skewness) was further studied using Cox regression model adjusting for confounding baseline variables. Results: 362 women participated in follow up. At a median follow up time of 9.5 years after rFNA sampling, 16 women developed invasive or non-invasive breast cancer. There were no significant differences between women who developed cancer and those that did not in regard to demographic factors, %breast density, MS, or Gail-LR. On univariate analysis, Gail-LR was higher in women who developed cancer (13.0 vs. 16.5, p=0.08). The largest hazard ratios were observed from high breast density (2.30, 95% CI 0.8, 6.6) and high CMI (2.26, 95% CI 0.8, 6.6, p=0.07). In breast cancer prediction, the AUC for CMI was 0.64 (95% CI 0.51, 0.77). In separate bivariable models that adjusted for age, Gail-LR, MS, and %breast density, the HR for log CMI was consistently above unity, with a p value consistently below 0.1, except for the model that included MS (see Table). Conclusions: Elevated CMI has potential as a robust predictor of future breast cancer occurrence in average risk women, even when adjusted for breast density or cytologic atypia. Our prior analysis established that CMI is not susceptible to variation with menstrual cycle phase and menopausal status. These features support its further evaluation in larger trials. Clinical trial information: NCT00896636 .[Table: see text]
Explainable prediction of survival using clinical, molecular, and radiomic profiles in recurrent high-grade glioma patients treated with CAR T-cell therapy.
Authors: Chi Wah Wong, Aleksandr Filippov, Kimberley-Jane C. Bonjoc, Christine Brown, Behnam Badie, Ammar Chaudhry
Journal: Journal of Clinical Oncology (2021)

104 Background: High-grade glioma (HGG) is an aggressive heterogeneous primary CNS neoplasm with high recurrence rate and poor survival. Multiple ongoing clinical trials are leveraging targeted molecular and immunologic therapeutics (e.g., pembrolizumab, Chimeric Antigen Receptor [CAR] T-cell therapy) in effort to improve survival. Explainable predictive models have shown value in identifying biomarkers predictive of treatment response as well as informing prognosis. In this study, we developed an explainable machine learning model leveraging clinical, molecular and radiomic (imaging) features to predict overall survival in patients suffering from HGG treated with CAR T-cell therapy. Methods: In this IRB-approved phase 1 clinical trial, 60 patients (39 males, median age = 49) suffering from HGG underwent surgical resection and CAR T-cell therapy 1 . All patients underwent baseline MRI scans prior to both surgical resection and CAR T-cell administration in the resection cavity. Using contrast-enhanced T1-weighted MRIs, we segmented the enhancing tumor (ET) and generated radiomic features. For predictive modeling, we incorporated the following features: Age, gender, race, ethnicity, histology, tumor grade (WHO), IL-13 receptor alpha 2 (IL-13Rα2) expression (H score), unifocal or multifocal lesions, tumor location (lobe), shape-based radiomics (tumor volume, surface area, and sphericity). We utilized gradient-boosted tree models to classify whether survival is above or below 180 days with two-loop nested cross-validation. For the inner validation loop, we optimized the model with hyper-parameter tuning. For the outer validation loop, we tested the optimal model on the hold-out data and the predictions were used as survival scores (0 – 1). Larger scores imply better predicted survival. For prediction explanations, we adopted the Shapley additive explanation (SHAP) framework. Results: The outer validation loop Area Under the Receiver Operating Characteristic Curve and Area under the Precision-Recall Curve were 0.76 and 0.81, respectively. Among the top five most important features calculated from SHAP; patients with larger tumor surface area, tumor volume and age have reduced survival scores while patients with larger IL-13Rα2 and tumor sphericity have increased survival scores. We stratified the patients into two distinct prognostic sub-groups (30 patients each group) using the survival scores obtained from the outer loop, with a log-rank test p &lt; 0.01. Conclusions: In patients with HGG treated with CAR T-cell therapy, we found that tumor surface area/volume and age are inversely related to survival while increased IL-13Rα2 expression and tumor sphericity were positive predictor of survival. Our model can potentially be used to optimize clinical trial enrollment through more precise patient screening and treatment planning.
A pilot study of the feasibility and utility of a fitness tracker to correlate activity level with patient reported outcomes (PROs) in sarcoma patients undergoing systemic therapy.
Authors: Elizabeth J. Davis, G. Dan Ayers, Deborah Wallace, Elizabeth Kaiser, Vicki Leigh Keedy, Rajiv Agarwal
Journal: Journal of Clinical Oncology (2021)

11559 Background: The feasibility and utility of wearable devices is unknown in sarcoma patients (pts). Objective assessment of activity level, body composition, and PROs facilitate understanding of the tolerability and toxicity of cancer treatment. Methods: From 6/11-10/12/2020, we enrolled sarcoma pts receiving systemic therapy to a prospective study evaluating activity levels and sleep via a Fitbit Charge 3, body composition with the Inbody 570, and PROs using NIH PROMIS short forms (fatigue, pain, physical function, and sleep disturbance), the Generalized Anxiety Disorder Scale, and the Patient Health Questionnaire Depression Scale. Time on study was 12-16 weeks depending upon treatment. The Fitbit was worn continuously. Body composition and PROs were assessed every 3-4 weeks. Feasibility was defined as successful device wearing and data syncing. Data was collected through a cloud-based application, Fitabase. Results: 22 pts were approached and enrolled. Two pts did not complete the first study assessment due to disease progression and were excluded from analysis. 50% of pts were female. 90% of pts were white. Median age was 47 yrs (range 20-81). The most common histologies were Ewing sarcoma and leiomyosarcoma. 89.5% (17/19) of pts wore the Fibit for &gt;3 weeks; median time was 68 days (5-112). 95% (19/20) of pts were able to sync data. Median step count was 2614 steps (376-19806). High step counts, defined as greater than the median, were associated with improved sleep (p=0.14) and physical function (p=0.22), and decreased pain (p=0.15), but these associations were not statistically significant. Low step counts, defined as lower than the median, were associated with skeletal muscle mass loss (p=0.22), but this was not statistically significant. Conclusions: Incorporating a fitness tracker is feasible in sarcoma pts receiving systemic therapy. It provides longitudinal, objective evaluation of activity levels and sleep patterns. Correlation of activity level with sleep, body composition, and PROs was limited due to small numbers; however, a larger prospective pilot study is ongoing.[Table: see text]
Artificial Intelligence for Automatic Measurement of Left Ventricular Strain in Echocardiography
Authors: Ivar M. Salte, Andreas Østvik, Erik Smistad, Daniela Melichova, Thuy Mi Nguyen, Sigve Karlsen, Harald Brunvand, Kristina H. Haugaa, Thor Edvardsen, Lasse Lovstakken, Bjørnar Grenne
Journal: JACC. Cardiovascular imaging (2021)

This study sought to examine if fully automated measurements of global longitudinal strain (GLS) using a novel motion estimation technology based on deep learning and artificial intelligence (AI) are feasible and comparable with a conventional speckle-tracking application. GLS is an important parameter when evaluating left ventricular function. However, analyses of GLS are time consuming and demand expertise, and thus are underused in clinical practice. In this study, 200 patients with a wide range of left ventricle (LV) function were included. Three standard apical cine-loops were analyzed using the AI pipeline. The AI method measured GLS and was compared with a commercially available semiautomatic speckle-tracking software (EchoPAC v202, GE Healthcare. The AI method succeeded to both correctly classify all 3 standard apical views and perform timing of cardiac events in 89% of patients. Furthermore, the method successfully performed automatic segmentation, motion estimates, and measurements of GLS in all examinations, across different cardiac pathologies and throughout the spectrum of LV function. GLS was −12.0 ± 4.1% for the AI method and −13.5 ± 5.3% for the reference method. Bias was −1.4 ± 0.3% (95% limits of agreement: 2.3 to −5.1), which is comparable with intervendor studies. The AI method eliminated measurement variability and a complete GLS analysis was processed within 15 s. Through the range of LV function this novel AI method succeeds, without any operator input, to automatically identify the 3 standard apical views, perform timing of cardiac events, trace the myocardium, perform motion estimation, and measure GLS. Fully automated measurements based on AI could facilitate the clinical implementation of GLS.
Time to discontinuation of opioids in patients with cancer after curative intent radiation.
Authors: Elena Valerie Fernandez, Alexander N. Slade, Julie Patterson, Pramit Nadpara, Darcy P. Mays, Norman Carroll
Journal: Journal of Clinical Oncology (2021)

e18692 Background: Many providers expect that cancer survivors would be able to discontinue opioids soon after treatment, although this has not been well studied. The time cancer survivors that received curative intent radiation (CIR) remain on opioids and associated factors were examined. Methods: Electronic medical record data of cancer survivors between January 1, 2008 and December 31, 2018 and Kaplan Meier survival models were used to estimate time to discontinuation (TTD) of opioids. Cox proportional hazards models were employed to identify factors associated with TTD. Results: Median TTD was 16.8 months (95% CI: 13.1-19.1 months) following CIR and shorter for patients without opioid exposure prior to therapy (new persistent opioid use [NPOU]; 13.0 months, 95% CI: 10.0-17.3 months) compared to patients with opioid exposure prior to therapy (chronic opioid use [COU]; 21.4 months, 95% CI: 17.5-28.8 months) (p-value = 0.0004). NPOU (HR: 1.35, 95% CI: 1.07-1.71) compared to COU and head and neck (HR: 1.60, 95% CI: 1.01-2.53) in comparison to breast cancer were associated with shorter TTD. Surgery (HR: 0.68, 95% CI: 0.50-0.91), death (HR: 0.55, 95% CI: 0.34-0.91), alcohol use (HR: 0.63, 95% CI: 0.42-0.95) and nicotine use (HR: 0.78, 95% CI: 0.62-0.98) were associated with longer TTD. Conclusions: Cancer survivors receive opioids for almost 1.5 years after CIR. Patients receiving surgery and using alcohol or nicotine are at higher risk. Patients with NPOU or head and neck cancers have shorter TTD. Evidence-based guidelines for opioid use in cancer survivors are warranted due to opioid use following CIR.