tbuckley/cabot-search huggingface dataset:
Value of cabozantinib in the treatment of advanced metastatic clear cell renal cell carcinoma (ccRCC): Real-world data from a single Korean institution.
Authors: Seoyoung Lee, Seul-Gi Kim, Sejung Park, Jeehyun Lee, Seung-Hoon Beom, Sang Joon Shin, Sun Young Rha
Journal: Journal of Clinical Oncology (2021)

e16578 Background: Cabozantinib is a multitarget tyrosine kinase inhibitor and getting attention in these days through its combination with immune checkpoint inhibitors. In this article, we analyze the efficacy of cabozantinib in patients with metastatic ccRCC in Korean who had progression after 1 or more VEGFR TKI therapies. Methods: Seventy-five patients from Jan.2019 to Dec. 2021 at Yonsei Cancer Center who had received cabozantinib treatment in second to fourth line of therapy were retrospectively reviewed. The primary endpoint was PFS. The secondary outcomes were the response rate, disease control rate (DCR), and OS. The evaluable subjects for efficacy were those who had at least one response evaluation. Results: Among 75 patients, 57 (76.0%) were male and median age was 59 years (range 33-81). Median follow up time was 12.1 months. There were 22 (29.3%) patients of second line, 38 (50.7%) of third line and 15 (20.0%) of fourth line of treatment. Median PFS was 5.6 months (95% CI, 4.6-6.6). Median OS was 13.6 months (95% CI, 5.0-22.2). The PFS based on the line of treatment was 4.7 months for second line, 5.6 months for third line and 12.0 months for 4th line. Proportion of patients who were previously treated with ICI was different between treatment line groups and showed increasing trend toward later line; 13.6% of second line, 31.6% of third line, and 66.7% of fourth line, respectively. The objective response rate was 8.0% with 6 patients of partial response. The DCR was 69.3%. The major toxicities were similar with the western population and most of them were less than CTCAE grade 3. Most common grade 3 or 4 AEs were anemia, hand-foot syndrome, fatigue, and stomatitis. There were no grade 5 AEs. Conclusions: Our results demonstrate that cabozantinib is an effective treatment option after first line TKI in Korean ccRCC patients with manageable toxicities. Notably, its tolerability in the advanced line of treatment and synergy with ICIs are suggested in this study despite heterogeneous patients of real world setting. This is the first real world data with cabozantinib in Asian patients.
Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes.
Authors: Vishwajith Sridharan, Mari Mino-Kenudson, James M. Cleary, Osama E. Rahma, Kimberly Perez, Jeffrey William Clark, Douglas Adam Rubinson, Lipika Goyal, Fateh Bazerbachi, Motaz Qadan, Aparna Raj Parikh, Cristina R. Ferrone, Brenna Casey, Carlos Fernandez Del-Castillo, David P. Ryan, Keith Lillemoe, Andrew Louis Warshaw, Kumar Krishnan, Yasmin Hernandez-Barco
Journal: Journal of Clinical Oncology (2021)

e16253 Background: Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series. Methods: This is a retrospective study conducted at a large healthcare system from 1996-2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test. Results: Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery conferred OS benefit in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy provided OS benefit in metastatic disease (p &lt; 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006). Conclusions: Pancreatic ACC patients often present with advanced disease. Surgery confers survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.
Outcomes of pancreatic ductal adenocarcinoma (PDAC) patients treated with neoadjuvant stereotactic body radiation therapy (SBRT) or conventionally fractionated radiation therapy (CFRT).
Authors: Fan Zhu, Haoyu Wang, Hani Ashamalla
Journal: Journal of Clinical Oncology (2021)

e16209 Background: Hypothesis: Neoadjuvant SBRT can improve survival when compared to CFRT in PDAC patients who received chemotherapy. Past retrospective studies have shown improved outcomes of definitive SBRT when compared to CFRT without accounting for chemotherapy. 1 We aim to study the outcomes of neoadjuvant SBRT vs CFRT accounting for chemotherapy. Methods: The National Cancer Database (NCDB) was queried for cases of PDAC from 2004-2015. Patients who received surgery and chemotherapy were included. Exclusion criteria were prior hormonal therapy or immunotherapy, lack of pathological confirmation or lack of information about chemotherapy. Log-rank test and Cox proportional hazards model were used to compare survival by radiation modalities. Predictors for overall survival (OS) were identified. Propensity score-matched (PSM) analysis balancing for different variables including type of chemotherapy was conducted. Results: Among 1604 patients, 223 (13.9%) had SBRT, and 1381 (86.1%) had CFRT. The median survivals were 30.0 and 26.0 months ( P = 0.010), while the 2-year survival rates were 63.4% and 53.7% for SBRT and CFRT patients, respectively. SBRT tended to be offered to older patients (age≥65: 56.1% vs 47.3%, P = 0.018), healthier patients (CCI=0: 72.2% vs 63.6%, P = 0.016), patients with worse cT staging (cT3 and cT4: 80.7% vs 69.7%, P = 0.008) and patients who got more multi-agent chemotherapy (89.2% vs 50.5%, P &lt; 0.001). In the cohort with positive clinical lymph nodes (cN+), CFRT tended to decrease the pN staging more when compared to SBRT ( P = 0.032) (Table). In multivariate analysis, multi-agent chemotherapy (HR, 0.72; P &lt; 0.001) was associated with better OS. SBRT did not show significantly better OS when compared to CFRT (HR, 0.81; P = 0.13) after accounting for other covariates including chemotherapy. PSM (1:1 match) analysis matched 223 pairs. SBRT did not show significant OS benefit (HR, 0.80; P = 0.17) when compared to CFRT. Conclusions: SBRT may be superior to CFRT in univariate analysis. However, after accounting for multi-agent chemotherapy, there is no significant survival difference between neoadjuvant SBRT and CFRT. Studies with larger sample size are desired. Neoadjuvant CFRT offers more significant nodal down-staging in patients with clinically positive lymph nodes (cN+) when compared to SBRT. Reference: Zhong J, Patel K, Switchenko J, et al. Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotacticbody radiation therapy versus conventionally fractionated radiation. Cancer2017 Sep 15;123(18):3486-3493. pN staging of cN+ cohort[Table: see text]
Using predictive models to determine the presence of non-small cell lung cancer metastasis to N2 and N3 regions.
Authors: Edward Hauptmann, Kiran Batra, Asha Kandathil, Arzu Canan, Sergio Alvarado, Qiubai Li, Vishal Kukkar, Yin Xi, Kemp H. Kernstine
Journal: Journal of Clinical Oncology (2021)

e20560 Background: Accurate assessment of non-small cell lung cancer (NSCLC) mediastinal involvement is key to developing treatment plans and determining prognosis. To date, there is no reliable imaging-based means to determine the presence or absence of mediastinal involvement. Current computed tomogram (CT) and fluorodeoxyglucose-positron emission tomography/ computed tomogram (PET-CT) technologies provide numerous derived automated variables have not been sufficiently evaluated to determine the presence of metastasis to the mediastinum. We have developed predictive models to determine the presence or lack of metastatic NSCLC in N2 and N3 regions. Methods: Consecutive patients from 2012-2017 with biopsy-proven NSCLC who had CT and PET-CT, as well as biopsy of the mediastinum had their images reread by a team of blinded specialty radiologists and nuclear medicine specialists. Patients with no mediastinal malignancy on biopsy were followed for 6 months from the initial evaluation to confirm lack of mediastinal malignancy.278 regions (N2 and N3) from 139 patients were included. Logistic regression models were used to build a baseline model, as well as models with additional nodal station maximum standard uptake valuve (SUV m ) measurements (SUV m , SUV m -SUV meanbloodpool and SUV lymph node/tumor (LN/T)) for N2 and N3 regions, respectively. When nodal station SUVm was not measured, SUV meanbloodpool was used. The SUVm within each region was used. Stepwise selection was used to select variables in the baseline model. Cross-validated ROC curve and area under the curve (AUC) were reported. All analyses were done in SAS 9.4 (SAS Institute, Inc., Cary, NC). Results: 40/139 N2 regions had malignancy, 4/139 N3 regions had malignancy. Baseline models for N2 regions selected lung laterality (OR right vs left: 4.84 (1.79, 13.05)) and nodal station short-axis diameter &gt; 1 cm (OR yes vs no: 5.49 (1.71, 17.54)) while no variables were selected for the baseline model for N3 regions due to lack of statistical power. We used the same variables for the N3 baseline model. Conclusions: We have identified models that use a more advanced analysis of predicting the presence or absence of metastatic NSCLC in both N2 and N3 regions with respect to the primary lesion. All models perform better with SUV m related measurements. From this information, we are developing a clinical application to provide practitioners a better means of assessing the presence of mediastinal involvement of NSCLC. [Table: see text]
Olaparib treatment (Tx) in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSR OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Overall survival (OS) results from the phase II LIGHT study.
Authors: Cara Amanda Mathews, Fiona Simpkins, Karen Anne Cadoo, Ying L Liu, Diane M. Provencher, Colleen McCormick, Adam ElNaggar, Alon D Altman, Lucy Gilbert, Destin Black, Nashwa Kabil, James Bennett, Jiefen Munley, Judy Yu, Carol Aghajanian
Journal: Journal of Clinical Oncology (2021)

5515 Background: LIGHT (NCT02983799) evaluated olaparib Tx in pts with PSR OC in cohorts with known BRCAm and HRD status. We report the final OS analyses. Methods: We conducted anopen-label, non-randomized, multicenter study of pts with PSR OC and ≥1 prior line of platinum-based chemotherapy (CTx). Pts were assigned to one of 4 cohorts: germline (g) BRCAm; somatic (s) BRCAm; HRD +ve (non-BRCAm); and HRD -ve. Genomic instability score (GIS) and gBRCAm status were determined by Myriad myChoice and BRACAnalysis CDx tests, respectively. HRD +ve tumors were defined by a GIS ≥42. Pts received olaparib Tx (starting dose 300 mg bid) until disease progression or unacceptable toxicity. OS was a secondary endpoint and was analyzed at 12 months (mo) after the primary analysis and 18 mo after the last pt was enrolled. Safety was assessed in pts who received ≥1 dose. Results: Data cut-off (DCO) was Aug 27, 2020. Of 272 enrolled pts, 271 received olaparib; of these, 270 had measurable disease at baseline and were included in efficacy analyses (Table). At DCO, 40% of pts had died (maturity) with a median follow-up in censored pts of 26.3 mo. Kaplan–Meier 18-mo OS rates were 86%, 88%, 79%, and 60% in the gBRCAm, sBRCAm, HRD +ve (non-BRCAm), and HRD -ve cohorts, respectively. Platinum-based CTx was the most common first subsequent Tx and was received by 39% pts after olaparib discontinuation. At DCO, the median duration of Tx was 7.4 mo and 244 pts had discontinued treatment, mainly due to disease progression (72%); 5% discontinued due to treatment-emergent adverse events (TEAEs). The only TEAE leading to discontinuation in &gt;1 pt was nausea (2 pts). Serious TEAEs were reported in 25% of pts. The most common serious TEAE was small intestinal obstruction (6%). Three adverse events of special interest occurred, each in 1 pt (&lt;1%): acute myeloid leukemia (post discontinuation), pneumonitis, and pulmonary fibrosis. Conclusions: In the final OS analysis, 18-mo OS ranged from 60–88% across the 4 cohorts. Consistent with the primary analysis, the 18-mo OS rate was highest in the BRCAm cohorts (similar OS in g and sBRCAm); among pts without a BRCAm, 18-mo OS was highest in the HRD +ve cohort. No new safety signals were observed compared with the primary analysis and with prior olaparib studies. Clinical trial information: NCT02983799. [Table: see text]
Health apps are designed to track and share
Authors: Quinn Grundy, Lindsay Jibb, Elsie Amoako, Geoffrey Fang
Journal: BMJ (2021)

Mobile health apps have generated substantial investment and enthusiasm for their potential to personalise interventions using real time user data.However, user data are not only invaluable for creating engaging and effective apps.Health apps are just one source of user data that is collected, transmitted to third parties, then aggregated to create detailed impressions about users and people such as them.These sources of big data are commercialised, often as consumer insights or algorithms, and used to deliver microtargeted adverts, influence political behaviours, or make decisions about health insurance, employment, and housing, 1 2 sometimes with exploitive or discriminatory effects. 3 Even so, users might reasonably assume that apps advertised for health purposes would treat health and personal information with greater care.To question this assumption, Tangari and colleagues (doi:10.1136/bmj.n1248)analysed more than 15 000 free Android apps in the "medical" and "health and fitness" categories of the Google Play store and compared their privacy practices with a random sample of more than 8000 apps from store categories unrelated to health. 4 They examined the apps' code to understand what kind of user data might be shared and with whom, and then during network traffic analysis which data were actually shared.Finally, they assessed users' awareness of privacy failings as expressed in app store reviews.
Cerium oxide nanoparticles loaded nanofibrous membranes promote bone regeneration for periodontal tissue engineering
Authors: Shuangshuang Ren, Yi Zhou, Kai Zheng, Xuanwen Xu, Jie Yang, Xiaoyu Wang, Leiying Miao, Hui Wei, Yan Xu
Journal: Bioactive Materials (2021)

Bone regeneration is a crucial part in the treatment of periodontal tissue regeneration, in which new attempts come out along with the development of nanomaterials. Herein, the effect of cerium oxide nanoparticles (CeO2 NPs) on the cell behavior and function of human periodontal ligament stem cells (hPDLSCs) was investigated. Results of CCK-8 and cell cycle tests demonstrated that CeO2 NPs not only had good biocompatibility, but also promoted cell proliferation. Furthermore, the levels of alkaline phosphatase activity, mineralized nodule formation and expressions of osteogenic genes and proteins demonstrated CeO2 NPs could promote osteogenesis differentiation of hPDLSCs. Then we chose electrospinning to fabricate fibrous membranes containing CeO2 NPs. We showed that the composite membranes improved mechanical properties as well as realized release of CeO2 NPs. We then applied the composite membranes to in vivo study in rat cranial defect models. Micro-CT and histopathological evaluations revealed that nanofibrous membranes with CeO2 NPs further accelerated new bone formation. Those exciting results demonstrated that CeO2 NPs and porous membrane contributed to osteogenic ability, and CeO2 NPs contained electrospun membrane may be a promising candidate material for periodontal bone regeneration.
Abstract NT-105: ANTI-TUMOUR EFFECTS OF ALL-TRANS RETINOID ACID, AN ANNEXIN A2-S100A10 PATHWAY INHIBITOR ON SEROUS OVARIAN CANCER
Authors: Noor A Lokman, Rachel Ho, Kavyadharshini Gunasegaran, Wendy M Bonner, Martin K Oehler, Carmela Ricciardelli
Journal: Clinical Cancer Research (2019)

Abstract Annexin A2 is increased in serous ovarian cancer and plays an essential role in ovarian cancer invasion and metastasis. In combination with S100A10, annexin A2 plays an important role in the plasminogen activator system regulating plasmin production. The aim of this study was to investigate the potential utility of all-trans retinoid acid (ATRA), an inhibitor of the annexin A2-S100A10 signalling pathway, as a new therapeutic against serous ovarian cancer. Survival of serous ovarian cancer cells (OVCAR-3, OV-90, &amp; OAW28) was significantly decreased by ATRA treatment (1-5µM). ATRA (1µM) also significantly decreased proliferation (Ki67 positivity, p=0.0034), S100A10 protein levels (p=0.0273), and increased cell apoptosis (cleaved caspase-3 positivity, p=0.0024) in serous ovarian cancer tissues using an ex vivo explant assay. In OAW28 cells, reduced cell survival following ATRA treatment was associated with a reduction of S100A10 protein levels, S100A10 and annexin A2 membrane localization, plasmin generation, motility and invasion. In contrast, ATRA inhibited OV-90 cell survival and invasion but did not affect plasmin activation or S100A10 and annexin A2 membrane localization or protein levels. These findings suggest that ATRA inhibits serous ovarian cancer proliferation and invasion via both S100A10 dependant and S100A10 independent mechanisms. Our results show that ATRA has promising potential as a novel therapy against serous ovarian cancer that warrants further evaluation. Citation Format: Noor A Lokman,Rachel Ho, Kavyadharshini Gunasegaran, Wendy M Bonner , Martin K Oehler, Carmela Ricciardelli. ANTI-TUMOUR EFFECTS OF ALL-TRANS RETINOID ACID, AN ANNEXIN A2-S100A10 PATHWAY INHIBITOR ON SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-105.
Association of plasma tumor DNA (ptDNA) with increased risk of venous thromboembolism (VTE) in metastatic castration resistant prostate cancer patients (mCRPC).
Authors: Vincenza Conteduca, Emanuela Scarpi, Daniel Wetterskog, Fabio Ferroni, Alice Rossi, Alessandro Romanel, Giorgia Gurioli, Sara Bleve, Caterina Gianni, Nicole Brighi, Giuseppe Schepisi, Cristian Lolli, Pietro Cortesi, Domenico Barone, Francesca Demichelis, Giovanni Paganelli, Himisha Beltran, Gerhardt Attard, Ugo De Giorgi
Journal: Journal of Clinical Oncology (2021)

5048 Background: Cancer is a risk factor for VTE. In mCRPC, ptDNA is an independent predictor of outcome ( Romanel, Sci Transl Med 2015; Conteduca, Br J Cancer 2020). We firstly aimed to investigate the association between ptDNA and VTE in mCRPC men treated with androgen receptor signaling inhibitors (ARSI) Methods: This prospective biomarker study included mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation. Targeted next-generation sequencing was performed to determine ptDNA fraction from pre-treatment plasma samples. Assessment of VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio (SHR) Results: Median age of 180 enrolled patients was 74 years (range 42-90). Of these, 60 (33.3%) were chemotherapy-naive. At a median follow-up of 58 months (range 0.5-111.0), 21 patients experienced VTE (venous thrombosis and/or pulmonary embolism) with a cumulative incidence of VTE at 12 months of 17.1% (95% CI 10.3-23.9). Before starting ARSI, ptDNA fraction above median value of 0.175, presence of visceral metastasis (mets), prior chemotherapy and serum lactate dehydrogenase (LDH) were significantly associated with higher incidence of VTE compared with patients with no thrombosis (12-month estimate, 18.6 vs 3.5%, P=0.0003; 44.4 vs 14.8%, P=0.015; 24.7 vs 4.5%, P=0.006; and 30.0 vs 13.5%, P=0.050, respectively). In the multivariate analysis (Table) including baseline ptDNA level, visceral, liver and lung mets, number of lesions, LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% confidence interval [CI] 1.63-20.44, P=0.006). All these patients received anticoagulant therapy for VTE. No ARSI discontinuation and VTE-related death were reported, and no significant difference in progression-free/overall survival was observed in mCRPC patients with and without VTE. Conclusions: These results suggest that baseline ptDNA fraction in mCRPC patients treated with ARSI is associated with increased risk of VTE. These patients may be followed up more closely for the risk of VTE and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA concentration. Validation of these findings in larger multicenter trials is warranted.[Table: see text]
Transcriptomic mapping on Notch signaling in A luminal phenotype breast cancer.
Authors: Katerin Ingrid Rojas, M Rocio Martín, Federico Rojo, Angelo Gámez-Pozo, Francisco J. De Castro, Elena Filipovich, Jaime Ceballos, M. Rosario Hernández, Jose Ales-Martinez
Journal: Journal of Clinical Oncology (2021)

e12539 Background: The Notch signaling pathway plays an important role in cell-differentiation, survival, proliferation, stem-cell renewal, and in determining cell fate during development and morphogenesis. The dysregulation of the Notch pathways contributes to carcinogenesis, cancer stem cell renewal, angiogenesis, and chemo-resistance. Elevated levels of Notch receptors and ligands have been associated with cancer-progression and poor survival. A less explored function of Notch pathways in cancer is their role in leukocyte homing and activation. Understanding their role and relationship with immune infiltrates is an area of interest in cancer research. Methods: The expression of four different Notch genes (Notch1, Notch2, Notch3 and Notch4) was explored in relation with A luminal breast cancer patient outcome using transcriptomic data (Affymetrix dataset, exploratory cohort) and the METABRIC study (validation cohort). The TIMER online tool was used to explore the association of the identified notch and immune infiltration, and the TCGA and METABRIC studies to analyze the correlation between notch1 - 4 expression and genomic signatures of immune activation. Results: We identified 2 individual genes called Notch1 and Notch2, which predict favorable prognosis in luminal A breast cancer. Their expression positively correlated with the presence of immune infiltrates within the tumor (dendritic cells, CD4+ T cells, neutrophils, CD8+ T cells and B cells), with markers of T cell activation and antigen presentation, and with gene signatures of immune surveillance (cytotoxic T lymphocyte activation and IFN gamma signature). By contrast Notch3 and Notch4 which predicted for detrimental outcome were not associated with any of these parameters. Conclusions: Our analysis identifies a Notch signature composed of 2 genes with potential to recognize immune infiltrated and activated A luminal phenotype breast cancers with favorable prognosis.