tbuckley/cabot-search huggingface dataset:
Mortality of multiple myeloma diagnosed peri-hospitalization.
Authors: Sam Rubinstein, Elizabeth Sigworth, Sandip Chaugai, Qingxia M Chen, Robert F. Cornell, Jeremy Lyle Warner
Journal: Journal of Clinical Oncology (2020)

e20553 Background: Although modern therapeutics for multiple myeloma (MM) have resulted in improved overall survival (OS) in recent years, patients who present with an acute disease-related complication often have poor outcomes. We sought to compare the OS of patients diagnosed with MM in or shortly after hospitalization with those diagnosed in the outpatient setting. Methods: Patients treated for MM at Vanderbilt University Medical Center (VUMC) between 2000 and 2018 were included. OS was computed from date of diagnosis; patients still alive were censored at date last known alive or of last follow-up. Baseline laboratory and cytogenetic data were used to calculate Revised International Staging System (R-ISS) stage; age was also recorded. Dates of inpatient notes and encounter codes were identified and compared to date of diagnosis to identify patients diagnosed within 30 days of an inpatient stay; patients whose first encounter at VUMC was 30 days or more after their diagnosis date were excluded. Cox proportional hazards modeling was performed to investigate the effects of a diagnosis within 30 days of an inpatient encounter controlling for age and R-ISS on OS. Time-dependent coefficients were included to investigate the effects of a peri-hospitalization diagnosis on OS before and after 90 days. Mortality at 90 days for each group was compared using Fisher’s exact test. Results: A total of 681 patients were included, of whom 81 (11.8%) were diagnosed peri-hospitalization. Patients diagnosed peri-hospitalization had inferior OS within the first 90 days (adjusted HR 8.38, 95% CI 4.22-16.66, p &lt; .001), but not after 90 days (Table). 90-day mortality for patients diagnosed peri-hospitalization was higher than for those not diagnosed peri-hospitalization (21.0% v. 3.3%, p &lt; 0.001). Conclusions: Patients diagnosed with MM peri-hospitalization had high early mortality in this study, although patients surviving more than 90 days have similar mortality to those diagnosed as outpatients. Many factors could account for this finding, such as irreversible renal failure or immobility due to MM, hospital-related complications, or more aggressive MM phenotype. Predictive models of early mortality in MM should account for inpatient status at diagnosis. [Table: see text]
Serum biomarkers of inflammation (ferritin, IL-8, TNFR1) and outcomes in BOLERO-2, a phase III trial of HR+/HER2- metastatic breast cancer treated with everolimus (mTOR inhibitor).
Authors: Suhail M. Ali, Albert Reising, Kim Leitzel, Joseph J. Drabick, Cristina I. Truica, Monali K. Vasekar, Harry Menon, Vinod Nagabhairu, Hyma Vani Polimera, Neha Pancholy, Prashanth Reddy Moku, Ashok Maddukuri, Herbert Schmid, Wei He, John Millholland, Meredith Lavin, Scott J. Hofsess, Robert William Sweetman, Gabriel N. Hortobagyi, Allan Lipton
Journal: Journal of Clinical Oncology (2020)

1067 Background: Everolimus (EVE) plus exemestane (EXE) doubled PFS while maintaining quality of life versus EXE alone in postmenopausal hormone receptor-positive (HR + ), HER2-negative metastatic breast cancer (MBC) (BOLERO-2 phase 3; NCT00863655). Here we investigated several serum biomarkers of inflammation: ferritin, interleukin-8 (IL-8), and tumor necrosis factor receptor 1 (TNFR1). Both higher IL-8 (ASCO 2018, #3025) and TNF (Nature 569:428-32, 2019) have been reported to be associated with worsened outcome to immune checkpoint inhibitors (ICI), and IL-8- and TNF-targeted therapies combined with ICIs are in phase I trials. We evaluated the prognostic/predictive ability of serum ferritin, IL-8, and TNFR1 to everolimus in BOLERO-2. Methods: Serum biomarkers were determined on pretreatment serum samples using the ELLA immunoassay platform (ProteinSimple, San Jose, CA). Cox-proportional hazards model was used to assess the efficacy of EVE, and the prognostic and predictive effect on PFS and OS. Results: Pretreatment serum biomarker levels were determined in 510 patients (70 %) of 725 BOLERO-2 patients randomized 2:1 to EVE+EXE or EXE). Serum levels (25%, 50%, 75%) were: ferritin (68.9, 125.5, 253.1 ng/ml); IL-8 (14.5, 19.4, 27.7 pg/ml); and TNFR1 (1205, 1470, 1868 pg/ml). Ferritin correlated significantly with TNFR1 (r=0.45, p&lt;0.0001), while IL-8 correlated weakly with TNFR1 (r=0.10, p=0.023). Higher levels of all 3 biomarkers were prognostic for significantly shorter PFS and OS (table). But no biomarkers were predictive: everolimus was efficacious regardless of the 3 biomarker levels (p&gt;0.05). Conclusions: High levels of serum ferritin, IL-8, and TNFR1 were significantly associated with shorter PFS and OS in HR+/HER2- MBC patients. Everolimus had superior outcomes compared to placebo, regardless of serum biomarker level. These 3 significant prognostic biomarkers are all associated with increased inflammatory processes through different pathways. Anti-inflammatory therapy targeted against these biomarkers should be evaluated based on serum level as potential combination therapy with everolimus or CDK 4/6 inhibitors in HR+ MBC. [Table: see text]
Antitumor activity of tipifarnib and PI3K pathway inhibitors in HRAS-associated HNSCC.
Authors: Francis Burrows, Shivani Malik, Zhiyong Wang, Stacia Chan, Silvio Gutkind
Journal: Journal of Clinical Oncology (2020)

e15658 Background: HRAS is an important driver oncogene in HNSCC and other squamous cell carcinomas (SCCs). HRAS mutations are observed in 6-10% of HNSCC cases and appear to define a unique subset of HNSCC associated with wild-type TP53, co-mutations in caspase 8 and a characteristic methylation pattern. RAS proteins undergo several posttranslational modifications that facilitate their attachment to membranes. The first and most critical modification is the addition of a farnesyl isoprenoid moiety by the enzyme farnesyltransferase (FT), prompting the development of FTIs for the treatment of RAS-driven cancers. Tipifarnib is a potent and selective FTI that has demonstrated compelling antitumor activity in a heavily pretreated cohort of recurrent/metastatic HNSCC carrying HRAS mutations. Based on these data, a pivotal study (NCT03719690) evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN) is currently ongoing. Methods: HRAS is the predominant RAS in squamous epithelial cells and SCCs commonly overexpress the protein. In TCGA PanCancer Atlas, approximately 30% of HNSCC cases have elevated HRAS gene expression, raising the possibility that some HRAS wild-type (WT) HNSCCs may also display a degree of dependence on this oncoprotein. The PI3K-AKT-mTOR pathway is another prominent driver in HNSCC, and reports suggest HRAS and PI3K can each drive resistance to inhibitors of the alternative pathway. In this study we explored the activity of tipifarnib in cellular models and six HRAS-mutant and twelve HRAS WT HNSCC patient-derived xenograft (PDX) models alone and in combination with inhibitors of PI3K-a (BYL-719), AKT (GSK2141795) and mTORC1/2 (INK128). Results: Tipifarnib induced regression in several HRAS WT-overexpressing models. In those cases where the FTI was only moderately active, robust inhibition of tumor growth was observed in the majority of animals treated with the combination of tipifarnib and the PI3K-a inhibitor BYL-719. Similar activity was noted in a smaller panel with GSK2141795 &amp; INK128. Regressions with the FTI-PI3K-a inhibitor doublet were observed both in tumors that were WT or harbored hotspot mutations or amplification of the PIK3CA gene and in HRAS mutants that carried or lacked PIK3CA mutations. Conclusions: Concomitant blockade of both targets may have surprisingly broad and potent anti-tumor activity in HNSCC. Additional biomarkers associated with sensitivity or resistance and alterations in gene expression (by RNAseq) and oncogenic signaling following treatment either as a monotherapy or in combinations will also be described.
External radiofrequency as a novel extracorporeal therapy for emphysema
Authors: Takeyuki Wada, Jen-erh Jaw, Masashi Tsuruta, Konosuke Moritani, Mai Tsutsui, Anthony Tam, Dragoş M. Vasilescu, Chung Yan Cheung, Kei Yamasaki, Samuel Lichtenstein, Lindsay Machan, Dan Gelbart, S. Paul Man, Don D. Sin
Journal: European Respiratory Journal (2020)

<b>External percutaneous application of radiofrequency (RF) energy improved lung compliance by selectively heating emphysematous tissues and inducing mild fibrosis. RF treatment is a potential novel therapy for extracorporeal treatment of pulmonary emphysema.</b>https://bit.ly/2ZbWgSk
Application of GAD-7 in population screening for generalized anxiety disorder
Authors: Yanyan Zhou, Yahong Bi, Limin Lao
Journal: BMJ (2018)

Generalized anxiety disorder (GAD) is one of the most common anxiety disorders. However, the diagnosis of GAD is difficult, GAD has the lowest diagnostic reliability among anxiety disorders and is often neglected. This article reviews the application of the General Anxiety Disorder-7 (GAD-7) in population screening for GAD, focusing on its history of development and the scope of unilization.


Key words: 
Generalized anxiety disorder; 7-items Generalized Anxiety Disorder Scale(GAD-7)
Effect of growth differentiation factor 15 (GDF-15) inhibition on energy balance in cancer cachexia and in lipopolysaccharide (LPS)-induced sepsis mouse models.
Authors: Danna Breen, Donald Bennett, Srinath Jagarlapudi, Stephanie Joaquim, Chang Zou, Anita Patel, Zhidan Wu, Randy Seeley, Bei Betty Zhang, Olivier Bezy
Journal: Journal of Clinical Oncology (2020)

e24153 Background: Growth differentiation factor 15 (GDF-15) is a cytokine that induces anorexia, weight loss and has been reported to be associated with cachexia and poor survival in illnesses characterized by inflammation such as cancer cachexia and heart failure. In preclinical cancer cachexia models, GDF-15 inhibition has been demonstrated to reverse cachexia and improve survival. Circulating GDF-15 is also elevated in patients with sepsis and is associated with increased complications and poor survival. However, the role of infection- and sepsis-induced GDF-15 in mouse models is controversial based on published reports. Methods: In this study, we examined the effect of GDF-15 inhibition on tumor and lipopolysaccharide (LPS)-induced anorexia, weight loss, and survival using a GDF-15 neutralizing antibody (mAB2) and GDF-15 knockout mice. Results: mAB2 efficacy was confirmed by reversing AAV-GDF-15-induced weight loss in wildtype mice. A cachectic (anorexia and weight loss) mouse tumor model was established with subcutaneous implantation of mouse renal cell carcinoma (RENCA) cells. The chemotherapy sorafenib was administered to slow tumor progression. Plasma GDF-15 was increased to ~2 ng/mL, similar to levels in cancer patients. Treatment with mAB2 rapidly reversed both anorexia and weight loss in the tumor-bearing mice. LPS injection (intraperitoneal, 5 mg/kg) increased circulating GDF-15 in wildtype mice reaching concentrations like that reported in septic patients within 90 minutes and remaining elevated after 48 hours (~1 ng/mL). LPS decreased food intake, body weight, and increased mortality (~20%). Different from the tumor model, GDF-15 neutralization with mAB2 did not prevent or exacerbate any of the effects of LPS. There were no observed detrimental effects of mAB2 treatment in either model. Similarly, in GDF-15 knockout mice the LPS effect on energy balance and survival was comparable to that observed in wildtype controls. Plasma GDF-15 was undetectable in the GDF-15 knockout mice. Conclusions: Taken together, these data suggest that GDF-15 is a critical regulator of energy balance and survival in selective pathophysiological states associated with weight loss.
A phase II trial of cabozantinib in hormone receptor-positive breast cancer with bone metastases.
Authors: Jing Xu, Michaela Jane Higgins, Sara M. Tolaney, Steven E. Come, Matthew Raymond Smith, Monica N. Fornier, Umar Mahmood, Beow Y. Yeap, Bruce Allan Chabner, Steven J. Isakoff
Journal: Journal of Clinical Oncology (2020)

1062 Background: We assessed the antitumor activity of cabozantinib, a potent multi-receptor oral tyrosine kinase inhibitor with activity against MET, RET, VEGFR2, and AXL, in patients with hormone-receptor positive (HR+) breast cancer with bone metastases. Methods: In this single-arm multicenter phase II study, patients with HR+, HER2- metastatic breast cancer and ≥ 1 prior line of therapy received an initial starting dose of 100 mg cabozantinib, later reduced to 60 mg per day. The primary endpoint was bone scan response rate determined by independent central review and defined as percent change of bone scan area from baseline. The target bone scan response rate was 30% compared to a null response rate of 10%. Secondary endpoints included objective response rate (ORR) by RECIST v1.1, progression free (PFS) and overall survival (OS). Bone scan and CT were obtained every 12 weeks. Results: Among 52 enrolled patients, median age was 55, and 54% and 42% had &gt; 2 lines prior endocrine and chemotherapy, respectively and 18 (35%) had bone-only disease. 20 (38%) experienced a partial bone scan response and 6 (12%) had stable disease (SD). 16 (31%) patients discontinued study prior to week 12 assessment for early clinical progression or toxicity, and three (6%) had missing follow-up scans. Best extra-osseous overall response revealed SD in 26 (50%), but no objective responses. In 25 patients with bone scan disease control at 12 weeks, only 3 (12%) developed extra-osseous progression. Median PFS was 4.3 months (90% CI 2.8 - 5.5) and OS was 19.6 months (90% CI 18.0 – 26.8). In a landmark analysis, patients with bone scan disease control at 12 weeks had longer OS (median 24.2 months, 90% CI 16.4 – 31.7) than those without (median OS 13.3 months, 90% CI 9.5 – 18.2), with a hazard ratio of 0.37 (90% CI 0.21 – 0.65). Most common grade 3 or 4 toxicities were hypertension (10%), anorexia (6%), diarrhea (6%), fatigue (4%) and hypophosphatemia (4%). Dose reduction or delay occurred in 42 (81%) patients. Conclusions: This study met its primary endpoint with bone scans improved in 38% of patients with metastatic HR+ breast cancer and remained stable in an additional 12% with cabozantinib treatment. Bone scan response correlated with improved OS. This is the first reported study in breast cancer to use bone scan response as a primary endpoint. Further studies with cabozantinib in HR+ breast cancer and additional validation of bone scan response as a surrogate for clinical benefit in breast cancer are warranted. Clinical trial information: NCT01441947 .
Geographic disparity of outcome in patients with cancer over decades: The surveillance, epidemiology, and end results.
Authors: Kenichi Sakurai, Hagop M. Kantarjian, Koji Sasaki, Elias Jabbour, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William G. Wierda, Naval Guastad Daver, Koichi Takahashi, Kiran Naqvi, Courtney Denton Dinardo, Guillermo Montalban Bravo, Ghayas C. Issa, Preetesh Jain, Sherry A. Pierce, Kelly A Soltysiak, Guillermo Garcia-Manero, Martha S Tingen, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2020)

1574 Background: Improvements in prevention, early detection and therapy of cancer have decreased cancer related mortality yet health disparities continue to exist. We investigated the impact of such disparities in cancer survival. Methods: In the Surveillance, Epidemiology, and End Results, we identified 784,341 patients with cancer from 1990 to 2016 in Georgia; 68,493 in 1990-1999, 371,353 in 2000-2009, and 322,932 in 2010-2016. We assessed overall survival (OS) of patients with all cancers, chronic myeloid leukemia (CML), and lung cancer given the dramatic improvement in patient outcomes in CML since 2000 compared to the consistently poor outcome in lung cancer. We assessed distance from each county to the one National Cancer Institute-designated cancer center (NCI-CC) in Georgia. Results: The 5-year OS of patients with any cancer was 55% with median OS 80 months; the 5-y OS of each county ranged from 33% to 82% (interquartile range[IQR], 51%-65%)(P &lt; 0.001). The improvement of OS was minimal over decades: 5-year OS was 52%, 55%, and 55% in 1990-1999, 2000-2009, and 2010-2016, respectively; the median was 69 months, 80 months, not reached, respectively (P &lt; 0.001). In patients with lung cancer and CML, the 5-year OS was 15% and 52% with the median of 9 months and 67 months, respectively. The geographic difference between counties was relatively small and constant over time in patients with lung cancer, represented by the width in the range and IQR: range 5%-17%, IQR 9%-13%, median 13% in 1990-1999; range 2%-24%, IQR 10%-14%, median 14% in 2000-2009; and range 4%-24%, IQR 12%-17%, median 17% in 2010-2016. However, the geographic difference was more prominent in patients with CML and widened after introduction of modern therapy: range 20%-42%, IQR 26%-34%, median 32% in 1990-1999; range 14%-83%, IQR 38%-64%, median 53% in 2000-2009; and range 14%-80%, IQR 40%-57%, median 57% in 2010-2016. Multivariate Cox regression showed age (hazard ratio[HR],1.040;95% confidence interval[CI],1.039-1.040;P &lt; 0.001), median county income (HR,0.919;95% CI,0.916-0.921;P &lt; 0.001), African American (HR,1.021;95% CI,1.210-1.227;P &lt; 0.001), and distance to NCI-CC (each 100 kilometers) (HR,1.021;95% CI,1.017-1.025;P &lt; 0.001) as predictive factors. Conclusions: The disparity of cancer care exists between geographic locations. The geographic difference of survival seems more prominent when highly effective therapies are available.
Impact of medical social work service package on service efficiency and patient satisfaction in general practice outpatient service
Authors: Yao Li, Mei Feng, Zhizhong Wang
Journal: BMJ (2018)

Objective
To evaluate the effects of medical social workers on the service efficiency and patient satisfaction in general practice outpatient service.


Methods
A randomized controlled intervention study was conducted at general practice department of Shanxi Dayi Hospital in June 2017. Three hundred and thirty patients were randomly selected and assigned into two groups: 159 patients received intervention with medical social work service package (intervention group) and 163 patients served as controls. The service package included advising service, counseling service, accompanying service, comfort service, intervention guidance service, etc. The average time per visit and patient satisfaction were compared between two groups and the effectiveness of intervention was evaluated by interview of doctors.


Results
There were no statistically significant differences in gender, age, occupation and insurance categories between the two groups (P>0.05). The average time per visit patients in the intervention and control groups were 18 (15, 22) min and 21 (15, 25) min, respectively (Z=2.364, P=0.018). The highest degree of patient satisfaction in the control group was the attitude of  (36/40, 90.0%), and the lowest was in the setting of consulting room (20/40, 50.0%). The highest degree of satisfaction in the intervention group was the comfortable with doctors (40/40, 100.0%), followed by the affinity nature of social workers (38/40, 95.0%), and the lowest was the environmental satisfaction index (32/40, 80.0%). The satisfaction of comfortableness with doctors, clinic environment and consultation process in intervention group [(40/40, 100.0%)、(32/40, 80.0%)、(37/40, 92.5%)] was higher than that in control group [(29/40, 72.5%)、(20/40, 50.0%)、(30/40, 75.0%)] (χ2=12.754, 7.912, 4.501, P<0.05).


Conclusion
Intervention provided by medical social workers can improve the efficiency of general practice outpatient service and improve the satisfaction of patients.


Key words: 
Social work; Outpatient service; General practice
Plasma IL-8 and PD-L1 and overall survival in metastatic castration-resistant prostate cancer patients (mCRPC).
Authors: Hyma Vani Polimera, Mark Pomerantz, Kim Leitzel, Subrina Farah, Wanling Xie, John A. Steinharter, Grace Shaw, Suhail Ali, Joseph J. Drabick, Neha Pancholy, Harry Menon, Matthew Tyler Bartock, Neal Shah, Prashanth Reddy Moku, Ashok Maddukuri, E. Scott Halstead, Todd Umstead, Daniel McKeone, Howard Spiegel, Allan Lipton
Journal: Journal of Clinical Oncology (2020)

e17565 Background: We previously reported the significant prognostic and predictive utility of pretreatment serum PD-L1 in the CCTG MA.31 breast cancer serum bank (SABCS 2018, abstr PD3-10). IL-8 (CXCL8) is a pro-inflammatory cytokine that binds to CXCR1 and CXCR2 and promotes tumor immune escape and progression. High serum IL-8 levels are associated with poor prognosis in many cancers, and have recently been reported to predict for reduced overall survival (OS) to nivolumab in lung cancer and melanoma (ASCO 2018, abstr #3025). Here we correlated plasma IL-8 and PD-L1 levels with OS in mCRPC patients. Methods: 201 metastatic CRPC patients had EDTA plasma available for this retrospective analysis. Patient eligibility included chemotherapy-naive mCRPC patients. The ELLA immunoassay platform (ProteinSimple, San Jose, CA) was utilized to quantitate plasma IL-8 and PD-L1. Cox regression assessed hazard ratio (HR) for OS using both categorical (median) and continuous (log-transformed) biomarkers. Results: In univariate analysis, higher plasma IL-8 levels were significantly associated with reduced OS when analyzed as a continuous variable (HR = 1.53; p = 0.003) and were of borderline significance at the median cutpoint (HR = 1.32; p = 0.069; 20.9 vs 31.5 mos median OS). Plasma PD-L1 levels were not significantly associated with OS when analyzed as a continuous variable (p = 0.17), but increased levels were significant when analyzed at the median cutpoint (HR = 1.36; p = 0.044; 21.9 vs 29.0 mos median OS). When plasma IL-8 and PD-L1 levels were combined (median cutpoints), plasma IL-8 high / PD-L1 high patients (n = 58) had a significantly shorter OS vs the plasma IL-8 low / PD-L1 low patients (n = 58) (HR = 1.69; p = 0.009; 19.3 vs 32.9 mos median OS, respectively). In multivariate analysis, when adjusted for biopsy Gleason score, age, PSA, and ECOG PS (all at time of blood draw), only high plasma IL-8 (on a continuous basis) was significantly associated with reduced OS (HR = 1.43; p = 0.019). Conclusions: In mCRPC patients, high plasma IL-8 and PD-L1 levels were associated with reduced OS (separately and combined). Circulating IL-8 and PD-L1 evaluation may inform prognosis in mCRPC and could be considered as biomarkers in future studies determining response to immune checkpoint inhibitor and anti-IL8 therapy.