tbuckley/cabot-search huggingface dataset:
Efficacy of sorafenib in symptomatic patients with pretreated progressive desmoid tumors.
Authors: Ferhat Ferhatoglu, Nail Paksoy, Izzet Dogan, Naziye Ak, Metin Pehlivan, Meltem Ekenel, Mert Basaran
Journal: Journal of Clinical Oncology (2021)

e23556 Background: Desmoid tumor (DT) is a rare disease characterized by histologically monoclonal fibroblastic proliferation. DT does not have metastatic spread potentially but can be infiltrative and locally aggressive and decrease patients' quality of life. Although current treatment guidelines recommend active surveillance as initial therapy, systemic therapy should be considered in rapidly progressing or symptomatic patients. Systemic treatments for DT include hormonal blockade, cytotoxic chemotherapy, and tyrosine-kinase inhibitors. In this real-life study, we aimed to evaluate the efficacy of sorafenib in patients with progressing or symptomatic DT. Methods: The clinical, pathological, and treatment data of the patients were retrospectively evaluated. Also, prognostic parameters for overall survival were assessed. We used SPSS v.25 for statistical analysis. Kaplan-Meier and Cox-regression analysis were used for survival analysis. Results: Seventeen patients were included in the study. The ratio of female/male patients was 2.4, and the median age was 32 (range,14-65). Four (23.5%) patients had Gardner syndrome. The rates of extra-abdominal and ıntra-abdominal tumor locations were 64.7% and 35.3%, respectively. The median follow-up duration before sorafenib was 6±0.84 years. Before sorafenib, 15 patients had underwent surgical resection. Four (23.5%) patients received adjuvant radiotherapy. All patients received median two-line systemic therapy, and four (23.5%) patients had received chemotherapy. The median treatment duration of sorafenib was 23.4±2.2 months. One- and two-year progression-free survival ratios were 94.1% and 80.7%, respectively. Grade 3-4 toxicities were observed in six (35.2%) of the patients. In univariate analysis, we found that gender (p = 0.012), ECOG performance status (p = 0.032), and history of Gardner syndrome (p = 0.021) were statistically significant prognostic factors for progression-free survival. However, there was no statistically significant between extra-abdominal and ıntra-abdominal tumor locations (p = 0.56). Conclusions: In the study, we observed that sorafenib was an effective treatment option for previously treated advanced desmoid tumors. Despite a small number of patients, we detected that male gender, poor ECOG performance status, and history of Gardner syndrome were negative prognostic factors for progression-free survival.
FOXA1 overexpression suppresses interferon signaling and immune response in cancer
Authors: Yundong He, Liguo Wang, Ting Wei, Yu-Tian Xiao, Haoyue Sheng, Hengchuan Su, Daniel P. Hollern, Xiaoling Zhang, Jian Ma, Simeng Wen, Hongyan Xie, Yuqian Yan, Yunqian Pan, Xiaonan Hou, Xiaojia Tang, Vera J. Suman, Jodi M. Carter, Richard Weinshilboum, Liewei Wang, Krishna R. Kalari, Saravut J. Weroha, Alan H. Bryce, Judy C. Boughey, Haidong Dong, Charles M. Perou, Dingwei Ye, Matthew P. Goetz, Shancheng Ren, Haojie Huang
Journal: Journal of Clinical Investigation (2021)

Androgen receptor–positive prostate cancer (PCa) and estrogen receptor–positive luminal breast cancer (BCa) are generally less responsive to immunotherapy compared with certain tumor types such as melanoma. However, the underlying mechanisms are not fully elucidated. In this study, we found that FOXA1 overexpression inversely correlated with interferon (IFN) signature and antigen presentation gene expression in PCa and BCa patients. FOXA1 bound the STAT2 DNA-binding domain and suppressed STAT2 DNA-binding activity, IFN signaling gene expression, and cancer immune response independently of the transactivation activity of FOXA1 and its mutations detected in PCa and BCa. Increased FOXA1 expression promoted cancer immuno- and chemotherapy resistance in mice and PCa and BCa patients. These findings were also validated in bladder cancer expressing high levels of FOXA1. FOXA1 overexpression could be a prognostic factor to predict therapy resistance and a viable target to sensitize luminal PCa, BCa, and bladder cancer to immuno- and chemotherapy.
The analysis of EGFR variants in Chinese adult glioblastoma patients.
Authors: Qiao Li, Weijie Sun, Yi Lu, Didi Guo, Tiantian Han, Guanghua Lu, Xiaomin Li, Ran Ding, Fanfeng Bu
Journal: Journal of Clinical Oncology (2021)

e14020 Background: Glioblastoma multiforme (GBM) is the most common primary brain tumor with complex genetic alterations and genomic profiles. EGFR amplification occurs in approximately 40% of primary GBM，EGFR mutation is also a prevalent genetic abnormality in GBM. A series of potential therapies targeting EGFR variants are currently in development, such as tyrosine kinase inhibitors (TKIs), monoclonal antibodies, vaccines, etc. However, to date, EGFR-targeted therapy continues to face significant challenges. A deeper understanding of EGFR variant profiles and pathobiology of GBM will be required. Methods: Next-generation sequencing of 131-gene profiling was performed to analyze EGFR activating mutations from 891 Chinese glioma patients in 2019-2020. Somatic mutations and copy number variations were detected following the standard operating procedure (SOP). We screened out the EGFR activating mutation and calculated the mutation frequency and the tumor location. Results: 51 GBM patients had activating mutations. The average age was 49 years (range,25-73 years). Most of the tumors occurred in the cerebral hemisphere (56.9%), followed by ventricles (3.9%) and thalamus (3.9%), etc. 43/51 (84.3%) were accompanied by high-fold EGFR amplification. 9/12 (75%) were EGFR intracellular mutation occurs with EGFR amplification, 31/35 (88.6%) were EGFR extracellular mutation occurs with EGFR amplification. Moreover, 4 patients carried EGFR intracellular and extracellular mutation occurs with EGFR amplification. There was no significant difference between the ratio of intracellular mutations and extracellular mutations with EGFR amplification (P=0.3496). Conclusions: In our GBM patients, EGFR activating mutations were accompanied by high-fold EGFR amplification. As we know that, GBM benefit from EGFR-TKIs may be limited. Therefore, multi-targeted combination therapy research could be considered in the future.
Validation of AML-Score in older adults receiving daunorubicin/cytarabine liposome intensive induction chemotherapy for treatment of secondary acute myeloid leukemia.
Authors: Abigail Schmucker, Benjamin Leiby, Lindsay Wilde
Journal: Journal of Clinical Oncology (2021)

e19000 Background: The AML-Score has been validated to predict complete remission (CR) and early mortality (EM) in patients receiving traditional induction chemotherapies but not daunorubicin/cytarabine liposome (Vyxeos; Jazz Pharmaceuticals; Palo Alto, CA). We conducted a retrospective analysis to evaluate, among patients with newly diagnosed secondary acute myeloid leukemia (sAML) who received intensive induction with daunorubicin/cytarabine liposome, how accurately the AML-Score predictions associate with observed 1) CR after intensive induction and 2) EM within 60 days after induction initiation. Methods: We abstracted demographic and clinical data from consecutive patients receiving daunorubicin/cytarabine liposome at the Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital between September 2017 and November 2020. We used descriptive statistics with 95% confidence intervals (CIs) and receiver operating curves to characterize the associations between AML-Score predictions and observed rates of CR and EM. Results: In total, 40 patients were included for analysis. 27 (67.5%) were male, 27 (67.5%) were white, 36 (90.0%) were not Hispanic or Latino, and 28 (70.0%) were aged 60-72 years. Twenty-seven patients (67.5%) had a CR, and 4 (10%) experienced early mortality. Observed rates of CR and EM generally increased with increasing predicted risk (Table). The area under the curve was 0.75 (95% CI 0.60-0.90) for CR and 0.82 (95% CI 0.68-0.96) for EM. Conclusions: The AML-Score tool trends in the correct direction in terms of predicting rates of CR and EM, and thus may contribute to oncologist prognostication and treatment planning for patients receiving daunorubicin/cytarabine liposome. However, its clinical utility is limited by the fact that it may underestimate the risk of CR and overestimate the risk of EM. Further study in a larger cohort is needed to update the AML-Score to give accurate point estimates of CR and EM risk in this population. Predicted CR and EM versus Observed CR and EM.[Table: see text]
Real-world BRAF testing patterns for patients with metastatic colorectal cancer (mCRC), metastatic melanoma, and non-small cell lung cancer (NSCLC).
Authors: Michelle L. Edwards, Rebecca Levin, Anup Abraham, Diana T. Amari, John M. Kelton, Maria Cecilia Vieira
Journal: Journal of Clinical Oncology (2021)

e18778 Background: BRAF mutations are estimated to occur in up to 10% of people with colorectal cancer, 45% with melanoma, and 2-4% with NSCLC and generally represent a poor prognosis for these patients. The National Comprehensive Cancer Network (NCCN) recommends BRAF testing for patients with mCRC, melanoma and NSCLC, however adherence to guidelines and real-world testing rates are not well known. This study describes real-world BRAF testing rates among mCRC, m-melanoma and NSCLC patients. Methods: We performed a retrospective study of adult patients diagnosed with mCRC or m-melanoma from 1/2013 to 11/2020 in the nationwide Flatiron Health EHR-derived de-identified database and with NSCLC from 1/2013 to 11/2020 in the ConcertAI Definitive Oncology Dataset. We measured the proportion of patients receiving a BRAF test and timing of testing in relation to diagnosis and treatment line, concentrating the latter on a limited time frame when there was a stable period of testing (2018-2019 for mCRC and m-melanoma; 2018 for NSCLC). Results: We included 21,758 patients with mCRC, 4,276 patients with m-melanoma, and 12,236 patients with NSCLC of whom 52.7%, 92.0% and 17.2%, respectively, received a BRAF test. Testing rates for mCRC and NSCLC increased over time (mCRC: 27.3% in 2013, 49.9% in 2016, 71.4% in 2020; NSCLC: 6.4% in 2013, 13.5% in 2016 and 29.5% in 2018) and were relatively stable for m-melanoma (94.5% in 2013, 90.6% in 2016, 89.5% in 2020). Among BRAF-tested mCRC patients in 2018-2019 (70.3%, n=5,874), 7.8% were tested before metastatic (m-) diagnosis, with median time from test to m-diagnosis of 8.5 months; 32.1% on or after m-diagnosis and before 1L and 55.8% on or after 1L, with median time from m-diagnosis to test of 1.4 months. Among BRAF-tested m-melanoma patients in 2018-2019 (91.7%, n=1,174), 31.0% were tested before m-diagnosis, with median time from test to m-diagnosis of 9.5 months; 62.2% on or after m-diagnosis and before 1L and 2.5% on or after 1L, with median time from m-diagnosis to test of 0.0 months. Among BRAF-tested NSCLC patients in 2018 (29.5%, n=2,010), 3.0% were tested before earliest diagnosis, with median time from test to diagnosis of 0.3 months; 24.6% on or after earliest diagnosis and before 1L and 15.4% on or after 1L, with median time from diagnosis to test of 1.1 months. (For about 60% of the BRAF-tested patients, it was not possible to identify at which stage of treatment the test was conducted). Conclusions: BRAF testing rates were highest among m-melanoma patients, followed by mCRC and NSCLC. Testing rates for mCRC and NSCLC increased from 2013 to 2020, which may have been in response to guideline changes and availability of targeted treatments. The majority of BRAF testing occurred before 1L in melanoma and NSCLC, and on or after 1L in mCRC.
Utility and acceptability of the EXCEEDS algorithm for oncology stakeholders: Results of a Delphi study.
Authors: Kelley Renee Covington, Timothy F Marshall, Julia L Sharp, Tiffany Kendig, Grant Richard Williams, Mackenzi Pergolotti
Journal: Journal of Clinical Oncology (2021)

e13538 Background: The Exercise in Cancer Decision Support (EXCEEDS) algorithm is an evidence-based, risk stratified framework. This framework allows for enhanced decision making for exercise pre-participation medical clearance and triage to cancer rehabilitation or exercise services across the cancer continuum. We conducted a Delphi study to examine utility and acceptability of the EXCEEDS algorithm for oncology stakeholders. Methods: Delphi study participants were randomized to two case studies, then made pre-participation medical clearance (yes/no) and intervention triage recommendations (cancer rehabilitation, clinically-supervised exercise, cancer-specific community-based exercise, and unsupervised exercise) in two conditions: independent (IND) and using EXCEEDS. Immediately following, participants rated algorithm acceptability in four domains using 4-point Likert scales (1- strongly disagree, to 4- strongly agree). We dichotomously coded accuracy (correct/incorrect) for each medical clearance and triage recommendation, then calculated the proportion of correct answers for each case to determine accuracy. We compared triage decision time (seconds) between conditions (IND vs. EXCEEDS) using paired-samples t-tests. We calculated the proportion of participants who ‘agreed’ (i.e., score ≥3) with each acceptability domain. Results: Oncology stakeholders (N=33) were mostly female (69.7%), 35-44 years old (42.4%), located in the United States (60.6%), and had at least 10 years of experience (60.6%). When using EXCEEDS, accuracy for medical clearance decisions improved in 3 of 4 cases (75%), triage decision accuracy improved in 4 of 4 (100%) cases, and triage time (seconds) improved significantly in 3 of 4 cases (75%, p&lt;.05). Table shows average improvement in decision accuracy and triage time for each case study. Most participants agreed that the algorithm was acceptable in each domain: “meets my approval” (n=21, 63.6%), “is appealing” (n=29, 87.9%), “enjoyable to use” (n=19, 57.6%), and “welcomed in my discipline or practice” (n=24, 72.7%). Conclusions: Accuracy and efficiency of decision-making for medical clearance and triage to cancer rehabilitation or exercise services was enhanced when using the EXEECDS algorithm. Most participants agreed the algorithm was acceptable. Future research is needed to validate the tool and explore avenues for dissemination and clinical implementation. % difference between EXCEEDS and Individual condition (EXCEEDS – IND) for medical clearance decision, triage decision and mean (M) and standard deviation (SD) of triage decision time.[Table: see text]
Outcomes and applicability of a deep learning virtual tumor board (DLVTB) in community-dwelling colorectal cancer (CRC) patients.
Authors: Aakash Desai, Arturo Loaiza-Bonilla, Cagatay Culcuoglu, Kristin Johnston, Selin Kurnaz
Journal: Journal of Clinical Oncology (2021)

e18635 Background: With almost 85% of patients treated outside NCI-designated cancer centers, providing comprehensive, state-of-the-art cancer care to millions of patients in the U.S. remains a significant challenge. We aimed to combine cutting edge AI based technology of DLVTB with high value-added services to provide evidence-based care management recommendations and implementation support to the patients and physicians in the community. To further demonstrate the feasibility, reproducibility, scalability, and benefits of DLVTB, we evaluated key outcomes from incorporating DLVTB in a cohort of 35 patients with advanced colorectal adenocarcinoma (CRC). Methods: Our core-enabling technology is a deep learning based Natural Language Understanding Engine that employs (1) natural language processing for medical text digestion and structuring, (2) decision trees and multilayer perception models to produce evidence-based treatment protocols, and (3) natural language based report generation. The technology platform is combined with human support from oncology sub-specialists to deliver a comprehensive Interpretive Report with a prioritized list of recommendations for each patient. These recommendations are operationalized by a case management team to ensure care implementation and monitoring of outcomes. Results: Thirty-five patients with CRC were referred for incorporation of DLVTB into clinical practice. Median age of patients was 57 years with 68.6% males. About 88.6% of the patients were Stage IV and 82.9% were treated by community practice oncologists. Median time since diagnosis was 17 months (1-73 months). Overall, DLVTB-cohort demonstrated an increase in median Overall Survival of 12 months per patient in comparison with historical cohorts. More specifically, DLVTB recommended initial and/or additional biomarker testing for 71% of the patients with further precision oncology-guided treatment recommendation (e.g. an EGFR inhibitor) for 80% of the patients. 63% of the patients were eligible for at least one clinical trial. 58% of the trials identified were within proximity (≤50 miles) of the patient’s primary residence. Thus, DLVTB was able to identify a trial that did not require extensive travel, provided eligibility and actionability closer to the point-of-care. 14% of the DLVTB evaluated patients subsequently enrolled in the recommended clinical trial, far surpassing the national average (3%). Moreover, DLVTB recommended treatments achieved on average savings of $39,194 per patient which is 35% of the average drug cost per patient. Conclusions: Our results demonstrate the feasibility and benefits of incorporating DLVTB into clinical practice. The utilization of DLVTB as a clinical trial enrollment tool and an engine for development of pathways resulting in improved clinical outcomes, in a cost-effective, and innovative care delivery model.
Real-world evidence (RWE) study of CAR-T agents in leukemia and lymphoma patients.
Authors: Lincy S. Lal, Cori Blauer-Peterson, Stacey DaCosta Byfield, Jennifer Malin
Journal: Journal of Clinical Oncology (2021)

e19573 Background: Chimeric antigen receptor T (CAR T) cell products are considered gene treatments, producing long term results, with just one infusion. Real world evidence on the two available CAR T cell products, tisagenlecleucel (T) and axicabtagene ciloleucel (AC) are limited in leukemia and lymphoma patients, specifically at the individual product level. This study presents treatment outcomes and resource utilization of these products from a payer perspective. Methods: Patients with evidence of CAR T administration per claims algorithm and from documentation from a prior authorization program from January 1, 2017 to May 30, 2020 were included; the CAR T administration was the index event. Baseline demographics and clinical characteristics, healthcare resource utilization (HCRU) for the CART T administration and pre and post CAR T administration for a fixed 6-month period, and previous treatments were captured and presented by product, using descriptive analytics. Results: The study population included 148 patients, mean age (SD): 57.4 (16.9), with 34% female, and 64% Commercial patients versus 36% Medicare patients, with a mean follow-up of 319 days (SD: 210). There were 15 leukemia patients, 119 lymphoma patients, and 14 patients with other indication in the study population; 71(48%) had evidence of being on a clinical trial during the study. The mean Charleson Comorbidity score at baseline was 3.9. Major comorbidities included anemia (71%), diseases of the heart (72%). 29(20%) patients were treated with T of which 24% were for leukemia and 76% for lymphoma and 67 (46%) were treated with AC of which 100% were for lymphoma, and 52 (35%) patients did not differentiate between products. Majority of the CAR T administration took place inpatient (84%). Baseline 6-month HCRU was 52% ER visits and 59% hospitalizations, compared to post 6-month utilization at 45% ER visits and 49% hospitalizations for the total population. 118 (80%) patients had evidence of prior treatment indicating that the CAR T was at least in the second line setting or higher. The most common priming chemotherapy was cyclophosphamide-fludarabine in 69 (47%) patients. Of the total population, 72% did not have any evidence of further treatment in the available follow-up time, specifically, 47% in the leukemia and 76% in the lymphoma populations, respectively. Conclusions: Majority of patients have evidence of prior treatments before the CAR T index date, indicating relapse. There is evidence of decrease in the HCRU subsequent to treatment, compared to pre period and 72% do not have subsequent treatment in the available follow-up time, indicating a high level of efficacy.
Genetic variants involved in the cGAS-STING pathway to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from FIRE-3 and TRIBE trials.
Authors: Jingyuan Wang, Yi Xiao, Fotios Loupakis, Sebastian Stintzing, Hiroyuki Arai, Francesca Battaglin, Natsuko Kawanishi, Priya Jayachandran, Shivani Soni, Wu Zhang, Christoph Mancao, Chiara Cremolini, Volker Heinemann, Alfredo Falcone, Joshua Millstein, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2021)

3535 Background: The intracellular DNA sensor stimulator of interferon genes (STING) plays a vital role in anti-tumor immune responses by recognition of self-DNA from tumors and by-products of genomic instability. Activation of STING was reported to enhance cetuximab mediated natural killer cell activation and dendritic cell maturation. Previous reports suggested that polymorphisms of cGAS-STING can affect innate immune response. Therefore, we hypothesized that genetic variants in the cGAS-STING pathway may predict first-line treatment outcome in mCRC pts treated with bevacizumab/cetuximab-based chemotherapy. Methods: Genomic DNA from blood samples of pts enrolled in two independent randomized trials, FIRE-3 (cetuximab arm, n = 129; bevacizumab arm, n = 107) and TRIBE (bevacizumab arm, n = 215), was genotyped through the OncoArray, a customized array manufactured by Illumina including approximately 530K SNP markers. The impact on outcome of 7 selected SNPs in 3 genes involved in the STING pathway (cGAS, STING, IFNB1) was analyzed. Results: In the Cetuximab cohort, pts with STING rs1131769 any T allele (N = 29) showed significantly shorter overall survival (36.3 vs 56.07 months) compared to carriers of C/C (N = 95) in both univariate (hazard ratio [HR] = 2.08; 95% confidence interval [CI]: 1.06-4.07; p = 0.003) and multivariate (HR = 2.98; 95%CI 1.35-6.6; p = 0.00848) analysis; Pts carrying IFNB1 rs1051922 any A allele (N = 68) showed significant shorter progression-free survival (10.23 vs 14.1 months) than carriers of G/G (n = 59) in both univariate (HR = 1.87; 95%CI 1.26-2.78; p = 0.00163) and multivariate (HR = 2.03; 95%CI 1.25-3.3; p = 0.004) analysis. No association were observed in the bevacizumab cohort of TRIBE and FIRE-3. Conclusions: Our study demonstrates for the first time that STING and IFNB1 polymorphisms could predict outcomes of Cetuximab-based treatment in mCRC patients; These finding may provide insight for the combination of STING agonist and anti-EGFR treatment in mCRC patients.