tbuckley/cabot-search huggingface dataset:
The process of urinary bladder cancer recurrence in 33 patients with 113 tumors, analyzed by changes in IHC features of 80 pairs of subsequent tumors.
Authors: Sven Kurbel, Branko Dmitrovic, Mate Matić, Damir Vrbanec
Journal: Journal of Clinical Oncology (2021)

e16507 Background: The aim was to define IHC changes between the two subsequent urinary bladder cancers (UBC). Methods: IHC data on EGFR, HER2, HER3, Ki-67, MLH1, MSH2, MSH6 and PMS2 in 113 UHC from 24 male and 9 female patients (1 to six recurrences) were used. Except for the Ki-67 value, other markers were stratified: “0” for no positive cells; “1” &lt; = 10% positive cells; “2” 1%-30% positive cells; and “3” 31%-100% positive cells. Data of consecutive tumors were paired in 80 processes of recurrence (PoR). Changes between the latter and the former tumor were calculated: in +/- % for Ki-67 values, and as integer sums of absolute changes in expression for HER markers and for Lynch markers. EM clustering was applied for recognition of relevant IHC changes. Results: Three aspects were tested: the speed of recurrence, was it the first, or later recurrence and whether PoRs depended on the total number of tumors in that patient. Early and late PoRs clustered along the Lynch score, while the intermediate clustered along the delta Ki-67 value. The first PoRs clustered along the HER score and all subsequent PoRs depended on the Lynch score. Conclusions: Even in this limited group of patients Lynch and HER markers showed complex differences between early and late recurrent tumors. The speed of the recurrence and changes of IHC features depended mainly on the rate of change in Lynch markers, suggesting that they should be tested as predictors of UBC recurrence.[Table: see text]
A first-in-human phase dose-escalation study of YH002, a recombinant humanized agonistic anti-OX40 IgG1 monoclonal antibody, in patients with advanced solid tumors.
Authors: Vinod Ganju, Adam Cooper, Kate Wilkinson, John J. Park
Journal: Journal of Clinical Oncology (2021)

e14501 Background: YH002 is a recombinant humanized IgG1 antibody that targets the human OX40 receptor. Preclinical studies have demonstrated the specificity, potency, and anti-cancer efficacy of YH002 in a comprehensive panel. The totality of nonclinical data supports progression of YH002 into clinical studies in adult patients (pts) with advanced solid tumors. Methods: This is an ongoing phase 1 dose-escalation study. Patients with advanced or metastatic refractory solid tumors received YH002 as single agent by IV administration at 0.01 to12.0 mg/kg dose levels every 21 days (Q3W), to evaluate the safety, tolerability and preliminary efficacy. An accelerated titration dose escalation design followed by a traditional 3+3 dose algorithm were utilized to assess dose-limiting toxicity (DLT) and identify MTD and/or RP2D. Tumor assessments were performed per RECIST v1.1 every 9 weeks. Results: By December 31 2020, six patients were enrolled and treated at escalating dose levels of 0.01 (n=1), 0.03 (n=1), 0.1 (n=1) and 0.3mg/kg (n=3), with tumor types including colon cancer, thymic cancer, prostate cancer, colorectal cancer, breast cancer and bladder cancer. Median treatment duration was 10.2 weeks (range 2 – 18). The median age of patients was 67 years old (range 47-78). These patients had progressed after a median of 2 prior lines of available standard therapy. As of data cutoff, no dose limiting toxicities (DLTs), no Grade (G) 3 or above adverse events (AE) or AEs leading to treatment discontinuation were reported. Drug-related adverse events (AEs) were all G1/2 events and occurred in 4 patients, including 8 G1 AEs (pneumonitis, rash, pruritus, arthralgia, myalgia, fatigue, lethargy, rash pruritic) and 3 G2 AEs (1 pneumonitis and 2 fatigue). Out of 5 patients having tumor assessment by RECIST, one pt with Thymic SCC at 0.3 mg/kg had best response of stable disease at week 9, one pt with prostate cancer at 0.1 mg/kg experienced Non-CR/Non-PD, and rest of 3 pts experienced progressive disease. Conclusions: These preliminary results demonstrate that YH002 was safe and tolerable up to 0.3mg/kg. Updated safety and antitumor activity will be presented. Clinical trial information: NCT04353102.
Long-term results of simplified lymphatic microsurgical preventing healing approach (SLYMPHA) for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection.
Authors: Tolga Ozmen, Christina Layton, Orli Friedman-Eldar, Siarhei Melnikau, Susan Kesmodel, Eli Avisar
Journal: Journal of Clinical Oncology (2021)

514 Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. SLYMPHA is a safe and relatively simple method, which decreases incidence of LE dramatically. Our initial study showed an 88% decrease in clinical LE rate after a median follow up of 15 months. The aim of this study was to confirm these results after a longer follow up period. Methods: All patients, undergoing ALND between January 2014 and November 2020 were included in the study. During follow-up visits, tape-measuring limb circumference method was used to detect clinical LE. The incidence of clinical LE was compared between patients with and without SLYMPHA. Univariate and multivariate analysis were used to assess the role of other factors in the appearance of clinical LE. Results: 580 patients were included in the study. 35% of cohort underwent SLYMPHA. Mean follow-up time was 44 ±31.9 months. Patients, who underwent SLYMPHA, had a significantly lower LE rate (10% vs 26%; p=0.002; OR 0.4 [0.31-0.77]). Diabetes and removing ³22 lymph nodes also correlated with increased LE however this effect disappeared on multivariate analysis. Conclusions: SLYMPHA is a safe and relatively simple method, which continued its efficacy after 4-years follow up. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.[Table: see text]
Risk of hospital admission for patients with SARS-CoV-2 variant B.1.1.7: cohort analysis
Authors: Tommy Nyberg, Katherine A Twohig, Ross J Harris, Shaun R Seaman, Joe Flannagan, Hester Allen, Andre Charlett, Daniela De Angelis, Gavin Dabrera, Anne M Presanis
Journal: BMJ (2021)

Abstract Objective To evaluate the relation between diagnosis of covid-19 with SARS-CoV-2 variant B.1.1.7 (also known as variant of concern 202012/01) and the risk of hospital admission compared with diagnosis with wild-type SARS-CoV-2 variants. Design Retrospective cohort analysis. Setting Community based SARS-CoV-2 testing in England, individually linked with hospital admission data. Participants 839 278 patients with laboratory confirmed covid-19, of whom 36 233 had been admitted to hospital within 14 days, tested between 23 November 2020 and 31 January 2021 and analysed at a laboratory with an available TaqPath assay that enables assessment of S-gene target failure (SGTF), a proxy test for the B.1.1.7 variant. Patient data were stratified by age, sex, ethnicity, deprivation, region of residence, and date of positive test. Main outcome measures Hospital admission between one and 14 days after the first positive SARS-CoV-2 test. Results 27 710 (4.7%) of 592 409 patients with SGTF variants and 8523 (3.5%) of 246 869 patients without SGTF variants had been admitted to hospital within one to 14 days. The stratum adjusted hazard ratio of hospital admission was 1.52 (95% confidence interval 1.47 to 1.57) for patients with covid-19 infected with SGTF variants, compared with those infected with non-SGTF variants. The effect was modified by age (P&lt;0.001), with hazard ratios of 0.93-1.21 in patients younger than 20 years with versus without SGTF variants, 1.29 in those aged 20-29, and 1.45-1.65 in those aged ≥30 years. The adjusted absolute risk of hospital admission within 14 days was 4.7% (95% confidence interval 4.6% to 4.7%) for patients with SGTF variants and 3.5% (3.4% to 3.5%) for those with non-SGTF variants. Conclusions The results suggest that the risk of hospital admission is higher for people infected with the B.1.1.7 variant compared with wild-type SARS-CoV-2, likely reflecting a more severe disease. The higher severity may be specific to adults older than 30 years.
Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3.
Authors: Massimo Cristofanilli, Hope S. Rugo, Seock-Ah Im, Dennis J. Slamon, Nadia Harbeck, Igor Bondarenko, Norikazu Masuda, Marco Colleoni, Angela DeMichele, Sherene Loi, Hiroji Iwata, Ben O'Leary, Eustratios Bananis, Yuan Liu, Xin Huang, Sindy Kim, Mariajose Lechuga, Nicholas C. Turner
Journal: Journal of Clinical Oncology (2021)

1000 Background: In PALOMA-3, a randomized, double-blind, placebo-controlled, phase 3 study, PAL+FUL significantly prolonged progression-free survival (PFS) compared with placebo (PBO) + FUL (1-sided P&lt;0.0001). The final protocol-specified OS analysis, which was conducted with a median follow-up of 44.8 months (mo), showed improved OS with PAL+FUL vs PBO+FUL (median OS, 34.9 vs 28.0 mo; hazard ratio, 0.814 [95% CI, 0.644–1.029]; 1-sided P=0.0429). Here, we report the results from an OS analysis with a longer median follow-up of 73.3 mo. Methods: A total of 521 patients (pts) with HR+/HER2– ABC who had progressed on prior endocrine therapy were randomized 2:1 to PAL (125 mg/d orally, 3/1 week schedule) + FUL (500 mg intramuscular injection) or PBO+FUL. Investigator-assessed PFS was the primary endpoint; OS was a key secondary endpoint. An ad hoc OS analysis was performed when 393 events (75% of the total population) were observed. Circulating tumor DNA (ctDNA) analysis was conducted among pts who consented for this study. Results: Improvement in OS continues to be observed with longer follow-up, with a hazard ratio of 0.806 (95% CI, 0.654–0.994; 1-sided nominal P=0.0221). The 5-year OS rate was 23.3% (95% CI, 18.7–28.2) with PAL+FUL and 16.8% (95% CI, 11.2–23.3) with PBO+FUL. Favorable OS with PAL+FUL vs PBO+FUL was observed in most subgroups except among pts who were endocrine resistant or had prior chemotherapy for ABC. No new safety signals were identified. Eighteen pts remain on study treatment, including 15 (4.3%) on PAL+FUL and 3 (1.7%) on PBO+FUL. A post-study cyclin-dependent kinase 4/6 inhibitor was received by 20 pts (7.5%) in the PAL+FUL arm and 32 pts (22.2%) in the PBO+FUL arm. ctDNA analyses of tumor mutation profiles (ie, ESR1, PIK3CA, RB1) at the end of treatment and their effect on OS will also be presented. Conclusions: The clinically meaningful improvement in OS with PAL+FUL was maintained with &gt;6 years of median follow-up in pts with HR+/HER2– ABC who had progressed on prior endocrine treatment. Pfizer (NCT01942135) Clinical trial information: NCT01942135 .[Table: see text]
Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial
Authors: Daniel K Burns, Robert C Alexander, Kathleen A Welsh-Bohmer, Meredith Culp, Carl Chiang, Janet O’Neil, Rebecca M Evans, Patrick Harrigan, Brenda L Plassman, James R Burke, Jingtao Wu, Michael W Lutz, Stephen Haneline, Adam J Schwarz, Lon S Schneider, Kristine Yaffe, Ann M Saunders, Emiliangelo Ratti, Dag Aarsland, Oda Ackermann, Joscelyn Agron-Figueroa, Thomas Arnold, Peter Bailey, Clive Ballard, Scott Barton, Christine Belden, James Bergthold, Wendy Bond, Ronald Bradley, Walter Braude, Mark Brody, Richard Brown, James Burke, Joseph Butchart, Theresa Campbell, Sandra Carusa, Roger Clarnette, Robert Cohen, Peter Connelly, Jacquelynn Copeland, Elizabeth Coulthard, Jill Crusey, Craig Curtis, Virginia De Sanctis, George Demakis, Natalie Denburg, Mardik Donikyan, Rachelle Doody, Aaron Ellenbogen, Debra Fleischman, Agnes Floel, Concetta Forchetti, Nestor Galvez-Jimenez, Jerome Goldstein, Felicia Goldstein, Kathryn Goozee, Daniel Gruener, Jerry Halsten, Howard Hassman, Elliot Henderson, Heinz-Peter Herbst, Steve Higham, Ronald Hofner, DeRen Huang, Fraser Inglis, Clark Johnson, Joseph Kass, Gregory Kirk, Arne Klostermann, Alex Knopman, Anne Koplin, David Krefetz, Reto Kressig, Rosalyn Lai, Gigi Lefebvre, Gabriel Leger, Mark Leibowitz, Allan Levey, Thomas Leyhe, Scott Losk, Kara Lyons, Jane Martin, Paul Massman, Christopher McWilliam, Silvana Micallef, Lefkos Middleton, Hugh Miller, Jacobo Mintzer, Robert Mitchell, Ricky Mofsen, Andreas Monsch, Philip Moore, Donna Munic-Miller, Marshall Nash, Judith Neugroschl, Margaret Newson, Rupert Noad, Esteban Olivera, Amanda Olley, Omid Omidvar, Mario Parra, Stephen Pearson, Robert Perneczky, Oliver Peters, Guy Potter, Geraint Price, Vanessa Raymont, Linda Rice, Craig Ritchie, Aaron Ritter, Jennifer Robinson, Sylvia Robinson, Jeffrey Ross, Dan Rujescu, Marwan Sabbagh, Ahad Sabet, Laura Samson, John Sass, Manish Saxena, Frederick Schaerf, Eugen Schlegel, Raj Shah, Richard Shingleton, Hamid Sohrabi, Robert Stephenson, Liebhild Stratmann, Pierre Tariot, Stephen Thein, Haydn Till, Nancy Voight, Ralph Votolato, Lorna Wallace, David Watson, Alexander White, Michael Woodward, Edward Zamrini, Christina Zimmerman
Journal: The Lancet Neurology (2021)
Adjuvant-free peptide vaccine targeting Clec9a on dendritic cells can induce robust antitumor immune response through Syk/IL-21 axis
Authors: Shanshan Gou, Shuai Wang, Wenwen Liu, Guanyu Chen, Dongyang Zhang, Jiangfeng Du, Zhongyi Yan, Hongfei Wang, Wenjie Zhai, Xinghua Sui, Yahong Wu, Yuanming Qi, Yanfeng Gao
Journal: Theranostics (2021)

Dendritic cells (DCs) can process the antigens of cancer vaccine and thus stimulate the CD8
Efficacy of cetuximab after immunotherapy (IO) in advanced cutaneous squamous cell carcinoma (CSCC).
Authors: Julian Andres Marin-Acevedo, Bethany Withycombe, Youngchul Kim, Zeynep Eroglu, Joseph Markowitz, Andrew S. Brohl, Ahmad A. Tarhini, Kenneth Yee Tsai, Nikhil I. Khushalani
Journal: Journal of Clinical Oncology (2021)

9562 Background: Anti-PD1 (aPD1) monotherapy with cemiplimab-rwlc or pembrolizumab is now considered standard of care for first-line management of advanced CSCC not amenable to surgery or curative radiotherapy. Previously chemotherapy or anti-EGFR agents were commonly used for these patients albeit with modest efficacy and limited duration of response. In prospective evaluation, the overall response rate (ORR) to cetuximab was 28% with disease control rate (DCR) of 69% at 6 weeks. The efficacy of second-line treatment following primary or acquired resistance to aPD1 therapy is not known. We investigated the activity of cetuximab in patients who progressed on previous IO therapy. Methods: We performed a single institution retrospective review from 9/28/18 (US approval date of cemiplimab-rwlc for CSCC) through 11/30/20 of patients with locally advanced or metastatic CSCC who received cetuximab after prior IO therapy. We identified patients who received cetuximab either immediately following IO therapy (cohort A) or as a subsequent line not immediately following IO therapy (cohort B). Primary endpoint was ORR with secondary endpoints of DCR, survival and toxicity. Median follow-up and survival times were calculated using the Kaplan-Meier method. Results: Thirteen patients, median age 72 years (62-82), all Caucasian, and 11 males (85%) were included in this study. Eleven pts received cetuximab immediately post-IO progression; two had additional intervening therapy post-IO before receiving cetuximab. Three patients received concurrent radiotherapy (palliative or definitive) with cetuximab. The ORR to cetuximab was 54% (7/13) including 1 complete and 6 partial responses. The cumulative 6-month DCR was 77%. All responses were observed in cohort A; both patients in cohort B had progressive disease as best response. Six of 7 initial responses are ongoing, including 3 in whom cetuximab was discontinued. At a median follow-up of 9.1 months, the median PFS has not been reached for the entire cohort. There were no unanticipated toxicities to cetuximab with rash (77%) and hypomagnesemia (54%) being the most common adverse events. Conclusions: In advanced CSCC, cetuximab used immediately after progression on aPD1 therapy yields notably higher and durable overall response than previously reported in the pre-IO therapy era. If validated in a larger dataset, this should be the preferred therapy for second-line treatment in advanced CSCC. Further exploration into the mechanism of this high efficacy of anti-EGFR therapy post aPD1 therapy is warranted.
Potential of 1.3-diethylbenzimidazolium triiodide in experimental therapy for lung cancer.
Authors: Alla I. Shikhlyarova, Lidia K. Trepitaki, Irina V. Kaplieva, Elena M. Frantsiyants, Dmitry A. Kharagezov, Anton G. Milakin, Igor A. Leyman, Oleg N. Stateshny, Viktoriya L. Volkova, Yuriy N. Lazutin
Journal: Journal of Clinical Oncology (2021)

e15094 Background: The practice of thoracic oncology demonstrates that the lungs often become affected by cancer. The antitumor effect of chemoradiation therapy can be poor, and surgical treatment is associated with reduced functionality of the organ and therefore reduced quality of life of patients. Therefore, nonspecific agents are required that combine a pronounced antitumor effect and, at the same time, restore pulmonary tissue. Our purpose was to study the effects of 1,3-diethylbenzimidazolium triiodide in a rat model of lung cancer by morphological analysis of pulmonary tissues. Methods: An experimental model of lung cancer was created in 60 male and female rats by subclavian infusion of sarcoma 45 cell suspension in the saline at a dose of 0.5 ml (2×10 6 ). Iodine-containing preparation was administered enterally at 0.4 mg/kg daily for 5 days with a 2-day interval; treatment was started immediately after the intravenous injection of malignant cells, the therapy lasted for 8 weeks. The morphological control of the lungs was performed at decapitation of animals, tissue processing and staining, by light microscopy using the LEICA DM LS2 microscope with magnification of up to x100. Results: Hematogenous introduction of tumor cells into the lung caused hemorrhage, “acute swelling” of the alveoli, microabscesses, distelectasis, colonization of interalveolar septa with tumor cells and the formation of large metastatic foci. Involutive changes in the tumor tissue were noted together with signs of pulmonary regeneration: after 5 weeks of the treatment – pronounced activation of immune cells and occurrence of elastic fibers with reserve tortuosity; after 8 weeks - active proliferation of epithelial elements that form the bronchial-alveolar apparatus, an increase in surfactant activity in hypertrophied alveoli, and a significant strengthening of the elastic and collagen framework of the alveolar walls. Conclusions: Morphological correlates of the experimental effect of 1,3-diethylbenzimidazolium triiodide indicate its strong antitumor properties and potential for improving the recovery capabilities of the structure-forming elements of the lung.
An unmatched case-control study evaluating the relationship between cancer diagnosis and drinking water source on the lower Eastern Shore of Maryland.
Authors: Angela Marie DeRidder, Adeel Masood
Journal: Journal of Clinical Oncology (2021)

e22514 Background: The lower Eastern Shore of Maryland is an agricultural and rural region with high cancer rates. Prior research has suggested that cancer patients on the lower Eastern Shore of Maryland rely on residential private well water more than municipal water, and that cancer patients rely on residential private well water more than individuals in the general county population. The purpose of this unmatched case-control study was to further clarify the relationship between cancer diagnosis and residential private well water use. Methods: A water consumption survey was provided to new hematology/oncology clinic patients seen at a regional hospital on the lower Eastern Shore from October 2020 through February 2021. Participants were asked their age, county of residence, residential water source, daily tap water consumption, presence of a water filtration system, and current or prior cancer history. A case was defined as an individual using residential private well water, and a control was defined as an individual using municipal water. Fisher’s exact test and binominal logistic regression were used to evaluate the relationship between residential water source and cancer history. Results: 334 patients were surveyed and 270 were included in analysis, with 133 cases and 137 controls. Median age of cases was 64 years (SD ± 16.6) and median age of controls was 62 years (SD ± 16.87). Our study found that compared to individuals utilizing municipal water, individuals utilizing residential private well water were more likely to live in their homes for &gt; 5 years (61% vs. 46%, p = 0.015), drink tap water (61% vs. 41%, p = 0.015), and utilize a water filtration system (31% vs. 16%, p = 0.006). Controlling for age, subjects who reported drinking at least two glasses of unfiltered private well water per day were more likely to have a current or prior cancer diagnosis compared to individuals relying on municipal water (OR = 2.57; 95% CI: 1.07-6.12, p = 0.03). Among subjects who drank less than 2 glasses of tap water per day or utilized a water filtration system, there was no difference in cancer history between individuals utilizing private well water versus municipal water. There were no relationships between county of residency, length of home residency, and cancer diagnosis. Conclusions: Individuals on the lower Eastern Shore of Maryland who consume at least 2 glasses of private well water without a water filtration system were more likely to indicate a current or prior cancer history compared to individuals consuming at least 2 glasses of municipal water. Interpretation is limited by small sample size and lack of causality, however, the results signal a need for additional studies evaluating well water use and cancer risk in this region.
Using cross-species vaccination approaches to counter emerging infectious diseases
Authors: George M. Warimwe, Michael J. Francis, Thomas A. Bowden, Samuel M. Thumbi, Bryan Charleston
Journal: Nature reviews. Immunology (2021)

Since the initial use of vaccination in the eighteenth century, our understanding of human and animal immunology has greatly advanced and a wide range of vaccine technologies and delivery systems have been developed. The COVID-19 pandemic response leveraged these innovations to enable rapid development of candidate vaccines within weeks of the viral genetic sequence being made available. The development of vaccines to tackle emerging infectious diseases is a priority for the World Health Organization and other global entities. More than 70% of emerging infectious diseases are acquired from animals, with some causing illness and death in both humans and the respective animal host. Yet the study of critical host–pathogen interactions and the underlying immune mechanisms to inform the development of vaccines for their control is traditionally done in medical and veterinary immunology 'silos'. In this Perspective, we highlight a 'One Health vaccinology' approach and discuss some key areas of synergy in human and veterinary vaccinology that could be exploited to accelerate the development of effective vaccines against these shared health threats. Emerging diseases that affect humans often arise due to the crossover of infectious agents from animal reservoirs. In this Perspective, George Warimwe and colleagues discuss the concept of 'One Health vaccinology', an approach that aims to use key lessons from human and veterinary immunology to develop more effective vaccination strategies for emerging infectious diseases.