tbuckley/cabot-search huggingface dataset:
Characterization of metastatic spinal cord compression from prostate cancer.
Authors: Jianbo Wang
Journal: Journal of Clinical Oncology (2020)

248 Background: Spinal cord compression (SCC) is one of the most debilitating conditions in metastatic prostate cancer patients (pts). A comprehensive analysis of pts could shed lights on predisposing factors and help with devising new ways for early detection and prompt treatment. Methods: 52 pts with magnetic resonance imaging-confirmed metastatic SCC from prostate cancer were identified at MD Anderson Cancer Center. Characteristics including age, anatomical site, Gleason score, overall survival(OS), time to diagnosis of SCC, underlying gene mutations, numbers of bone metastasis, number of lines of treatment and clinical outcome were analyzed. Results: 96.15% of SCC occurred in thoracic spine in comparison to 74% as reported previously. At the time of diagnosis of SCC, median age is 70 years, median OS is 1537 days, median time to development of SCC is 1222.5 days, median lines of systemic treatment is 4, median PSA value is 66.4, 100% of pts have a Gleason score above 7, 94% of pts have &gt;4 bone metastasis, roughly 20% of pts had visceral metastases. 55% of 9 evaluable pts harbored P53 gene mutation. About 80% of pts received radiation treatment; 17% of pts received surgery; 49% of pts had fair clinical outcome after treatment (Table). Conclusions: The observed predominance of SCC in thoracic spine (96.15%) suggests an underlying mechanism governing development of SCC in preferential sites. Further research to define this mechanism will help with prevention, detection and treatment of SCC. Additionally, characterized potential predictive factors (Gleason score≥7, &gt;4 bone mets, presence of P53 mutation) could be used to develop an algorithm to improve the management of SCC.[Table: see text]
A geometrically adaptable heart valve replacement
Authors: Sophie C. Hofferberth, Mossab Y. Saeed, Lara Tomholt, Matheus C. Fernandes, Christopher J. Payne, Karl Price, Gerald R. Marx, Jesse J. Esch, David W. Brown, Jonathan Brown, Peter E. Hammer, Richard W. Bianco, James C. Weaver, Elazer R. Edelman, Pedro J. del Nido
Journal: Science Translational Medicine (2020)

A biomimetic prosthetic heart valve is geometrically adaptable to accommodate somatic growth and structural asymmetries within the hearts of sheep.
Prostate cancer survivorship care plans: What we are failing to tell men after treatment?
Authors: Youngjee Choi, Katherine C. Smith, Aishwarya Shukla, Amanda L. Blackford, Phuoc T. Tran, Kimberly S. Peairs, Thomas M. DeMarco, Amanda Choflet, Kristen Farling, Madeline Kelso, Michael Anthony Carducci, Nancy Mayonado, Elliott Tolbert, Claire Frances Snyder
Journal: Journal of Clinical Oncology (2020)

311 Background: Survivorship care plans (SCPs) present essential information about cancer treatment and follow-up recommendations for cancer survivors. We describe the completeness of prostate cancer SCPs and evaluate guideline concordance of follow-up recommendations. Methods: We analyzed 125 prostate cancer SCPs from an academic and community cancer center, abstracting demographics, cancer/treatment details and follow-up recommendations. Follow-up recommendations were compared to national guidelines. Results: Content provided in &gt;90% of SCPs included cancer TNM stage; PSA at diagnosis; radiation treatment details (98% of men received radiation); and PSA monitoring recommendations. Potential treatment-specific side effects were listed for 69% of men who had surgery, 78% for androgen deprivation therapy (ADT) and 97% for radiation. The presence of post-treatment symptoms were noted in 67% of plans – several ADT-related side effects (e.g., bone thinning, cognitive changes, muscle atrophy) were noted for 0/21 men who completed all ADT. Guidelines recommend an annual digital rectal exam (DRE) with no physical exam otherwise specified. No SCPs specified DRE, but all 68 SCPs at the community site recommended at least annual follow-up visits with urology, radiation oncology, and primary care. Only 5/57 SCPs at the academic site specified follow-up visits (radiation oncology every 6 months). Guidelines recommend PSA testing every 6-12 months (optional 3 months if high risk) for 5 years, then annually; while duration was not specified in any SCPs, if applied to the first 5 years, 91% of SCP recommendations were guideline concordant, 7% suggested oversurveillance, and 2% were incomplete. In men who received ADT, guidelines recommend assessing bone density (by imaging or FRAX score), and goal testosterone level. Of 80 men who completed or had ongoing ADT, 2% were recommended for bone density imaging (0 had FRAX scores) and 19% for testosterone levels. Conclusions: SCP content is more complete for demographic and treatment summary information with gaps in addressing treatment effects and follow-up recommendations beyond PSA testing. These findings highlight the need to improve the quality of information in SCPs. Clinical trial information: NCT03035773.
Efficacy and safety of traction-assisted endoscopic submucosal dissection: a meta-regression of randomized clinical trials
Authors: Ying-Fong Su, Sheng-Wei Cheng, Chun Chao Chang, Yi-No Kang
Journal: Endoscopy (2020)

Abstract Background Endoscopic submucosal dissection (ESD) is widely used to treat gastrointestinal lesions. A traction-assisted (TA) strategy has been recently developed for ESD. In this study, we evaluated the safety and efficacy of TA-ESD compared with conventional ESD (C-ESD). Methods We searched PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure to identify randomized clinical trials that compared TA-ESD and C-ESD. No filters for language or date of publication were used. Outcomes included complete resection rate, resected specimen size, procedure time, hemostasis usage (frequency), overall complication rate, perforation rate, and delayed bleeding rate. We used the mean difference (MD) for continuous outcomes in a random-effects model and Peto odds ratio (POR) for binary outcomes where any zero cell existed. Effect sizes and their 95 % confidence intervals (CIs) were determined. Results 12 out of 929 identified articles, including 1499 patients, were analyzed. According to pooled results, TA-ESD produced similar R0 resections to C-ESD, but its procedure time (minutes) was shorter than that of C-ESD (MD – 16.02, 95 %CI – 22.71 to – 9.33). Moreover, TA-ESD had a lower complication rate (POR 0.47, 95 %CI 0.29 to 0.76) and perforation rate (POR 0.24, 95 %CI 0.10 to 0.56) than C-ESD. A nonsignificant difference in delayed bleeding rate was observed, although there was a trend toward this being lower in TA-ESD than C-ESD (POR 0.90, 95 %CI 0.46 to 1.75, I 2 = 12 %). Conclusions The traction-assisted strategy improves safety and efficacy in the treatment of patients with ESD. However, we observed different effect sizes in the esophagus, stomach, and colorectum.
Pembrolizumab (pembro) plus enzalutamide (enza) for enza-resistant metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-199 cohorts 4-5.
Authors: Julie Nicole Graff, Emmanuel S. Antonarakis, Christopher J. Hoimes, Scott T. Tagawa, Clara Hwang, Deepak Kilari, AJ Ten Tije, Aurelius Gabriel Omlin, Raymond S. McDermott, Ulka N. Vaishampayan, Anthony Elliott, Helen Wu, Jeri Kim, Charles Schloss, Johann S. De Bono
Journal: Journal of Clinical Oncology (2020)

15 Background: KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study. Cohort (C)4 (RECIST-measurable disease) and C5 (bone-predominant disease) consist of chemotherapy-naive patients (pts) with mCRPC treated with enza + pembro after progression with enza. Results for C4 and C5 presented. Methods: Pts with or without prior abiraterone had clinically meaningful response/benefit to enza followed by disease progression. Pts received pembro 200 mg Q3W with continuation of enza for up to 35 cycles or until progression/intolerable toxicity. Primary end point: ORR, blinded independent central review (C4). Secondary end points: DCR, PSA response rate (≥50% reduction), rPFS, OS, and safety (C4, C5); DOR (C4). Results: Of 126 pts (C4, 81; C5, 45), 107 discontinued, primarily due to progression. Median follow-up: 13.7 mo (C4, 11.8; C5, 18.6). ORR (95% CI) for pts with measurable disease was 12% (6-22) in C4; DCR for all pts: 51% (39-62) in C4 and 51% (36-66) in C5 (Table). Any grade/grade 3-5 treatment-related AEs occurred in 75%/26% pts in C4 and 69%/24% in C5. Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any grade/grade 3-4 rash (regardless of treatment relatedness) was higher than previously reported for individual agents (33%/6%). All except one pt (grade 3 treated with IV steroids) were treated with oral/topical steroids or had no intervention. Conclusions: Addition of pembro to enza following enza resistance showed modest antitumor activity in pts with RECIST-measurable and bone-predominant mCRPC. Combination had manageable safety and is being evaluated in a phase 3 trial. Clinical trial information: NCT02787005. [Table: see text]
Dupilumab Efficacy in GINA-Defined Difficult-to-Treat Type 2 Asthma Patients
Authors: Klaus Rabe, J. FitzGerald, Eric Bateman, Mario Castro, Ian Pavord, Jorge Maspero, William Busse, Megan Rice, Yamo Deniz, Paul Rowe, Naimish Patel, Nikhil Amin, Marcella Ruddy, Neil Graham, Ariel Teper
Journal: Journal of Allergy and Clinical Immunology (2020)
The role of cytoreductive nephrectomy (CN) for patients with metastatic renal cell carcinoma (mRCC) in the setting of retroperitoneal lymphadenopathy: An analysis of the National Cancer Database (NCDB).
Authors: Akshay Reddy, Andrew D Sparks, Michael Joseph Whalen
Journal: Journal of Clinical Oncology (2020)

688 Background: Recent evidence has suggested systemic therapy alone (ST) may be comparable to CN in treating mRCC. This study aims to understand oncologic outcomes and survival of those with node positive mRCC treated with ST compared to CN and explore the role of LAD at the time of surgery. Methods: A retrospective cohort analysis of patients who had undergone either ST or CN for clinically node-positive mRCC was performed using the NCDB. The CN group was subdivided into no LND vs. LND (based on reported lymph node yield, “LNY” (i.e. 0 vs. ≥1). Demographic and clinicopathological variables were compared to adjust for confounding covariates in multivariable analysis. Patients who underwent palliative treatments or LAD without nephrectomy were excluded. Results: The majority of CN were performed via open approach (70.1%). CN was associated with decreased mortality hazard relative to ST, while no difference in survival was detected between LAD and no LAD (Table). Median LNY was 2. Inpatient stay was significantly longer for LAD relative to no LAD (median 5 vs. 4 days; P=0.02). CN was associated with increased odds of 30 day hospital readmission relative to ST (aOR=8.6; 95% CI: 5.5 – 13.4; P&lt;0.01), while LAD was significantly associated with decreased odds of 30 day hospital readmission relative to no LAD (aOR=0.6; 95% CI: 0.4 – 0.9; P=0.02). Conclusions: CN is associated with a significant survival advantage but potentially greater complications compared to those receiving ST in node-positive mRCC. Despite offering diagnostic information via a more aggressive approach, there does not appear to be therapeutic benefit of LAD with CN in the metastatic setting where patients receive concomitant ST.[Table: see text]
Regorafenib-loaded poly (lactide-co-glycolide) microspheres designed to improve transarterial chemoembolization therapy for hepatocellular carcinoma
Authors: Xiang Li, Guangwei He, Feng Su, Zhaoxing Chu, Leiming Xu, Yazhong Zhang, Jianping Zhou, Yang Ding
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Transarterial chemoembolization (TACE) has been widely introduced to treat hepatocellular carcinoma (HCC) especially for unresectable patients for decades. However, TACE evokes an angiogenic response due to the secretion of vascular endothelial growth factor (VEGF), resulting in the formation of new blood vessels and eventually tumor recurrence. Thus, we aimed to develop regorafenib (REGO)-loaded poly (lactide-co-glycolide) (PLGA) microspheres that enabled localized and sustained drug delivery to limit proangiogenic responses following TACE in HCC treatment. REGO-loaded PLGA microspheres were prepared using the emulsion-solvent evaporation/extraction method, in which DMF was selected as an organic phase co-solvent. Accordingly, we optimized the proportion of DMF, which the optimal ratio to DCM was 1:9 (v/v). After preparation, the microspheres provided high drug loading capacity of 28.6%, high loading efficiency of 91.5%, and the average particle size of 149 µm for TACE. IR spectra and XRD were applied to confirming sufficient REGO entrapment. The in vitro release profiles demonstrated sustained drug release of microspheres for more than 30 d To confirm the role of REGO-loaded microspheres in TACE, the cell cytotoxic activity on HepG2 cells and anti-angiogenic effects in HUVECs Tube-formation assay were studied in combination with miriplatin. Moreover, the microspheres indicated the potential of antagonizing miriplatin resistance of HepG2 cells in vitro. Pharmacokinetics preliminary studies exhibited that REGO could be sustainably released from microspheres for more than 30 d after TACE in vivo. In vivo anti-tumor efficacy was further determined in HepG2 xenograft tumor mouse model, demonstrating that REGO microspheres could improve the antitumor efficacy of miriplatin remarkably compared with miriplatin monotherapy. In conclusion, the obtained REGO microspheres demonstrated promising therapeutic effects against HCC when combined with TACE.
Extracellular cGAMP is a cancer-cell-produced immunotransmitter involved in radiation-induced anticancer immunity
Authors: Jacqueline A. Carozza, Volker Böhnert, Khanh C. Nguyen, Gemini Skariah, Kelsey E. Shaw, Jenifer A. Brown, Marjan Rafat, Rie von Eyben, Edward E. Graves, Jeffrey S. Glenn, Mark Smith, Lingyin Li
Journal: Nature Cancer (2020)
Tumor immune microenvironment alterations in penile squamous cell carcinoma using multiplex immunofluorescence and image analysis approaches.
Authors: Jad Chahoud, Frederico Netto, Rossana Lazcano Segura, Edwin Roger Parra Cuentas, Xin Lu, Priya Rao, Ignacio Ivan Wistuba, Curtis R. Pickering, Curtis Alvin Pettaway
Journal: Journal of Clinical Oncology (2020)

4 Background: Penile Squamous Cell Carcinoma (PSCC) is a rare but often fatal disease. In this study, we characterize the poorly understood immune microenvironment using multiplex immunofluorescence (mIF) and image analysis approaches in 54 patients with PSCC. Methods: Representative blocks of 54 PSCC patients were stained for six immune markers: CD3, CD8, CD68, PD-1, PD-L1, Pancytokeratin and DAPI. Two experienced pathologists using an image analysis system (InForm 2.2.4) divided them into the tumor and stroma compartment and assessed the different densities of cell phenotypes using R studio with results expressed as cells/mm2. The statistical correlations were performed using Fisher’s exact test, Pearson and Log-rank test for Kaplan Meyer plots. Results: 54 patients with confirmed diagnosis of PSCC had a median age of 62 (IQR 50-70). All samples were from the primary penile tumor with the majority of cases being HPV(–) (62%). We observed significantly higher stromal cytotoxic T cells in HPV(+) cases compared to HPV(–) ( P=0.04). Using the mean macrophage count as cutoff for positivity, high densities of total tumor macrophages CD68+ were associated with significantly improved estimated median cancer specific survival (CSS) (NA, P=0.04), median overall survival (OS) (68mos vs NA P=0.02) and lower risk of regional recurrence ( P=0.04). On the other hand, the high densities of stromal cytotoxic T cells antigen-experienced (CD3+CD8+PD-1+), was associated with significantly worse median OS (27 vs 102mos P=0.05) and median disease free survival (DFS) (18.2mos vs NA P= 0.07). Also, high densities of stromal T cells antigen-experienced (CD3+PDL-1+), were associated with significantly better CSS (NA, P=0.06) and better median OS (142.1 vs 68.8mos P=0.14). Conclusions: Using novel multiplex image analysis to assess the immune microenvironment in primary PSCC, we showed that high macrophage levels were associated with lower risk of recurrence and improved survival outcomes. Moreover, a low level of exhausted stromal cytotoxic PD-1+ T cells was associated with improved PSCC survival. Further characterization of T cell subsets in relation to tumor HPV status is ongoing.
Intravesical irrigation to prevent early bladder recurrence in patients undergoing laparoscopic radical nephroureterectomy for upper urinary tract cancer.
Authors: Takaaki Tamura, Shinichi Sakamoto, Satoshi Yamamoto, Maihulan Maimaiti, Yusuke Imamura, Akira Komiya, Maki Nagata, Tomohiko Ichikawa
Journal: Journal of Clinical Oncology (2020)

454 Background: The bladder carcinoma recurrence rate after nephroureterectomy is known to be high. Here we studied the clinical benefit of Intravesical irrigation during laparoscopic radical nephroureterectomy in upper urinary tract cancer (UUTUC) patients. Methods: This study enrolled 197 UUTUC patients who receive laparoscopic radical nephroureterectomy at Chiba University Hospital and Yokohama Rosai Hospital between 2001 and 2019. Association between the various clinical factors and postoperative recurrence rates within two years were statistically analyzed. Intravesical irrigation was carried out only during surgery and by using distilled water or saline. Results: Bladder recurrence was confirmed for 79 of the 197 patients. Irrigation was carried out in 75 cases (distilled water, 49 cases; saline, 26 cases). Tumor grade (G1-2 vs G3; p=0.0029) and irrigation (with vs. without; p&lt;0.0001) were related to bladder recurrence on univariate analysis. Even on multivariate analysis, both tumor grade (p=0.0094) and irrigation ( p&lt;0.0001) remained as independent factors. Comparison between the irrigation and non-irrigation groups showed that bladder recurrence rates were significantly lower in the irrigation groups (irrigation group vs non-irrigation group: 29.3% vs 46.7%, p=0.015). There was no prognostic difference between the type of irrigation (distilled water vs saline, p=0.177). Conclusions: Intravesical irrigation prevented early bladder recurrence in patients undergoing radical nephroureterectomy for UUTUC. [Table: see text]
An exploratory study of 89Zr-DFO-Atezolizumab ImmunoPET/CT in patients with locally advanced or metastatic renal cell carcinoma.
Authors: I. Alex Bowman, Marianna Dakanali, Aditi Mulgaonkar, Hans J. Hammers, Xiankai Sun, Orhan K. Oz, James Brugarolas
Journal: Journal of Clinical Oncology (2020)

TPS759 Background: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for renal cell carcinoma (RCC). Despite this, responses to single-agent anti-PD-1 occur in only 25% of patients. Biomarkers such as PD-L1 expression and tumor infiltrating lymphocyte density may predict response, but require invasive biopsies that fail to fully interrogate the complex tumor microenvironment throughout the patient. Efforts are underway to identify who will benefit from ICIs. Among these are the use of radiolabeled antibodies against PD-L1. We propose to combine the specificity of anti-PD-L1 antibodies with the sensitivity, resolution, and quantification offered by positron emission tomography to develop immunoPET (iPET). iPET will allow real-time monitoring of tumor and its microenvironment in-vivo, and may correlate with response and toxicity with ICIs. Methods: The anti-PD-L1 antibody Atezolizumab is conjugated to Zirconium-89 via desferrioxamine (DFO). 89 Zr-DFO-Atezolizumab will be administered to two cohorts of approximately 20 patients. Cohort 1 have localized RCC prior to undergoing surgery, and cohort 2 have metastatic RCC prior to treatment with an ICI. The main exclusion criteria are existing use of an ICI or comorbidities that would preclude treatment with an ICI. All subjects will receive an IV injection of 89 Zr-DFO-Atezolizumab followed 7 days (+/- 1 day) by a PET/CT scan. Subjects in cohort 2 will receive treatment with ICI per clinician discretion. Subjects will receive a repeat scan if disease recurrence is documented (cohort 1) or should progression or toxicity occur after treatment with an ICI (cohort 2). Biopsy of disease recurrence (cohort 1) will be standard, and encouraged for sites of disease progression on ICI (cohort 2). Co-primary endpoints are an exploratory analysis of 89 Zr-DFO-Atezolizumab uptake on PET/CT with PD-L1 expression assessed by IHC in patients undergoing surgery (cohort 1) and to evaluate uptake across metastatic sites and explore the relationship with response or toxicity with ICI therapy (cohort 2). An investigational new drug approval has been granted for 89 Zr-DFO-Atezolizumab (IND 143266) and accrual commenced 1 October 2019. Clinical trial information: NCT04006522.
Development of a predictive model of PSA response to a switch from prednisone to dexamethasone in metastatic castrate-resistant prostate cancer patients biochemically progressing on abiraterone.
Authors: Reeta Barua, Cameron Phillips, Vanessa Sarah Arciero, Liying Zhang, Amanda Rahmadian, Seanthel Delos Santos, Shruti Parshad, Urban Emmenegger
Journal: Journal of Clinical Oncology (2020)

88 Background: Abiraterone acetate (AA) is typically administered with prednisone (P) to prevent symptoms of mineralocorticoid excess in patients with metastatic castrate resistant prostate cancer (mCRPC). After biochemical progression on AA + P, there is a sizeable subset of patients who have a renewed PSA response when switched from P to dexamethasone (D). The purpose of this study was to delineate clinical and pathologic factors that are predictive of a PSA response to such a steroid switch. Methods: We performed a retrospective analysis of 87 patients switched from AA+P to AA+D at Sunnybrook Odette Cancer Centre (Toronto, ON, Canada) between December 2012 and September 2018. Information on demographics, disease characteristics, previous treatments and performance status was collected. Response to the P to D switch maneuver was defined as a decrease in PSA by ≥30% within 12 weeks of the intervention (PSA30). Univariate logistic regression analyses were used to create a prediction model for each covariate tested, and R 2 was applied for the measure of fit.Using multivariable logistic regression analysis and a backward stepwise selection procedure, we sought to identify patient and/or disease characteristics associated with a PSA30. Results: 38/87 patients (44%) experienced a PSA30. Univariate analysis showed that a favourable ECOG performance status, no prior docetaxel and no prior enzalutamide use were associated with a PSA30. On multivariable logistic regression analysis both favourable ECOG performance status and no prior enzalutamide use remained associated with a PSA30 (Table). Conclusions: A considerable proportionof patients with mCRPC who biochemically progress on AA+P have a renewed PSA response when changed to AA+D.Patients with a favourable ECOG performance status and no prior enzalutamide use are more likely to respond to such a steroid switch. Further prospective studies are needed to validate our findings.[Table: see text]
Moving the global disability agenda forward with scarce data
Authors: Anne Roca, Dominic Haslam OBE, Emma Jolley, Anna Ruddock, Elena Schmidt
Journal: The Lancet Global Health (2020)

We read with great interest the article by Jonathan Abuga and colleagues in The Lancet Global Health on excess mortality in children aged 6–9 years with neurological impairments in Kenya.1 The increased mortality risk borne by neurologically impaired children in that age group compared with their peers without disabilities is a finding that, even without elucidation of specific causes, is important for both advocacy and programming. In the absence of robust mortality registration and health information systems, describing these causes is obviously very challenging.