tbuckley/cabot-search huggingface dataset:
A prospective study of an AI-based breast cancer screening solution for resource-constrained settings.
Authors: Richa Bansal, Bharat Aggarwal, Lakshmi Krishnan
Journal: Journal of Clinical Oncology (2021)

e13586 Background: Screening mammography is often found to have low sensitivity in women with high density breast tissues. Alternate modalities of breast USG and MRI require high-quality expensive equipment making the regular screening with these modalities less affordable and accessible, particularly in resource-constrained settings This study evaluates the clinical performance of an AI-based test (Thermalytix) that uses machine learning on breast thermal images which could potentially be a low-cost solution for breast screening in low- and middle-income countries (LMICs). Methods: The prospective comparative study conducted from December 2018 to January 2020 evaluated the performance of Thermalytix in women with dense and non-dense breast tissue who presented for a health check-up at a hospital. All women underwent Thermalytix and mammography. Further investigations were recommended for participants who were reported as positive on either test. Sensitivity and specificity of Thermalytix were evaluated across age-groups, menopausal status, and breast densities. Results: Among the 687 women recruited for the study, 459 women who satisfied the inclusion criteria were included in the analysis. 168 women had ACR categories ‘c’ or ‘d’ dense breasts, of which 37 women had an inconclusive mammography report (BI-RADS 0). Overall, 21 women were detected with breast cancer in the study. Thermalytix demonstrated an overall sensitivity of 95.2% (95% CI, 76.1-99·9) and a specificity of 88.6% (95% CI, 85.2-91.4). Among women with dense breast tissue (n=168), Thermalytix showed a sensitivity of 100% (95% CI, 69.2-100) and a specificity of 81.7% (95% CI, 74.7-87.4). In women with ACR categories ‘c’ and ‘d’ dense breasts, mammography reported 22% of them as inconclusive (BI-RAD 0), while in the same sub-set of the population Thermalytix demonstrated a sensitivity of 100%. Conclusions: The AI-based Thermalytix demonstrated high sensitivity and specificity in the study cohort. It also fared well in women younger than 50 years and pre-menopausal women where routine mammography screening yields low sensitivity. Overall, this study introduces Thermalytix, a promising radiation-free, automated, and privacy-aware test that can supplement mammography for routine screening of women, especially in women with dense breast tissue, and has the potential to influence the clinical practice in LMICs by making breast cancer screening portable and affordable. Performance of Thermalytix and mammography in women with high breast densities (ACR categories ‘c’ and ‘d’ breasts). Clinical trial information: NCT04688086. [Table: see text]
Partha Kar: Imposter syndrome is no cause for shame
Authors: Partha Kar
Journal: BMJ (2021)

Imposter syndrome is no cause for shame Partha Kar consultant in diabetes and endocrinology How much of a problem for doctors is imposter syndrome?Is it just a term used by those who struggle to fit in?Is it a manifestation of totally natural self-doubt?Over the years we've lived with the rhetoric that successful people "don't show weakness" or "don't cry."When interacting virtually in the online world, it's far easier to make such judgments about others without knowing them as individuals.In doing so we may be reinforcing false beliefs or perhaps even forcing someone to conform to a set opinion or view.
Treatment patterns and outcomes of locally advanced gall bladder cancer: A National Cancer Database (NCDB) analysis.
Authors: Pragnan Kancharla, Lynna Alnimer, Yazan Samhouri, Karthik Shankar, Veli Bakalov, Thejus Thayyil Jayakrishnan, Chelsea Peterson, Deanna Huffman, Rodney E. Wegner, Dulabh K. Monga
Journal: Journal of Clinical Oncology (2021)

e16147 Background: Gall bladder (GB) cancer is rare but an aggressive disease especially when presenting at an advanced stage. There is controversy regarding the best treatment approach for locally advanced disease. In this NCDB analysis, we aim to study treatment patterns for T3, T4, and/or N1 GB cancer and estimate survival for each treatment modality. We also sought to investigate clinical and socioeconomic predictors of treatment selection. Methods: We conducted a retrospective cohort analysis using de-identified data accessed from the NCDB. The NCDB provided records of 39,229 patients diagnosed with GB cancer between 2004-2017. We excluded patients who were not treated at the reporting facility, those with no histologic confirmation of the diagnosis, those with no survival data available and those with T1, T2 and metastatic disease. We did exploratory analysis and divided patients into six arms based on treatment modality (Table). Stepwise multivariable regression models were used to analyze predictors of treatment selection. Survival estimates were calculated using the Kaplan Meier and proportional Cox hazard regression methods. Results: We identified 7,004 patients with GB cancer who fulfilled the inclusion and exclusion criteria. Median age was 68 years. There were 69.5% females, and the majority of patients were white (66.1%). Receiving treatment at an academic/research center (OR 0.37, 95% CI 0.19-0.73, p &lt;0.01), black patients (OR 0.55 95% CI 0.36-0.85, p &lt;0.01) and higher education (OR 0.58, 95% CI 0.37-0.91, p 0.02) decreased the odds of receiving surgery. Meanwhile, the presence of lymphovascular invasion was seen more amongst patients with receipt of surgery. For patients who underwent radiation, increasing age (OR 0.97, 95% CI 0.97-0.98, p &lt;0.01) and higher histologic grade (OR 0.65, CI 0.46-0.92, p .02) were associated with less radiation use. Median income between $50,354-$63,332 (OR 1.28, 95% CI 1.02-1.60, p 0.04) was associated with more radiation use. Patient who received triple therapy had improved survival compared with other modalities (HR 0.51, CI 0.46-0.57, p &lt;0.01). Median overall survival (OS) for the whole population was 13.0 months (CI 12.6-13.5) (Table) Conclusions: American patients with T3, T4, and/or N1 GB cancer received variable treatment modalities. Patients who underwent triple-modality therapy in our analysis had improved adjusted-overall survival compared with other modalities. Limitations include unmeasured confounding factors, selection bias and the retrospective design. We also identified clinical and socioeconomic factors that affect treatment selection.[Table: see text]
Clinical performance of blood-based RNA signatures (GemciTest) for the gemcitabine response in advanced pancreatic cancer.
Authors: David Piquemal, Roman Bruno, Florian Noguier, Fabien Pierrat, Amelia Gamez, Jerome Cros, Noelle K. LoConte
Journal: Journal of Clinical Oncology (2021)

e16238 Background: Pancreatic ductal adenocarcinoma (PDAC) is highly lethal often presents at a later stage. Gemcitabine is still an important component in PDAC treatment however there is no routine biomarker to predict its efficacy. We had previously performed a discovery cohort of two separate RNA-blood signatures in 60 patients (NCT00789633) showing an association with PFS and OS. Called GemciTest, this CE-IVD molecular test requires 2.5ml whole blood sample before starting the patient's 1st line chemotherapy. From this liquid biopsy, IVD measures the expression levels of nine genes using real-time PCR processes. This abstract presents the clinical validation of GemciTest. Methods: In this study, clinical validations were done on 214 patients (mean 68.7-year-old; 37-88) from 3 distinct cohorts with the University of Wisconsin Biobank, GemciPANC trial (NCT03599154), and BACAP (NCT02818829). These cohorts included first-line treatment,with either a gemcitabine or fluoropyrimidine based regimen. Results: Patients with a clinical benefit response identified by GemciTest (31.5%) had a significantly longer progression free survival (PFS) (5.4 months vs. 3.1 months p = 0.0032) and a longer overall survival (OS) (13.1 months vs. 5.4, p &lt; 0.0003). In multivariate analyses including tumor localization and performance status, this signature continued to be associated with PFS (HR = 0.52 (0.34–0.81) p = 0.003) and OS (HR = 0.44 (0.28 – 0.69) p = 0.0002).Conclusions: GemciTest validation was performed, showing a strong association with PFS and OS.[Table: see text]
Aggregation-induced emission luminogens for highly effective microwave dynamic therapy
Authors: Nil Kanatha Pandey, Wei Xiong, Lingyun Wang, Wei Chen, Brian Bui, Jian Yang, Eric Amador, Mingli Chen, Christina Xing, Aseem Atul Athavale, Yaowu Hao, Wirya Feizi, Lloyd Lumata
Journal: Bioactive Materials (2021)

Aggregation-induced emission luminogens (AIEgens) exhibit efficient cytotoxic reactive oxygen species (ROS) generation capability and unique light-up features in the aggregated state, which have been well explored in image-guided photodynamic therapy (PDT). However, the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications. Coincidentally, microwaves (MWs) show a distinct advantage for deeper penetration depth in tissues than light. Herein, for the first time, we report AIEgen-mediated microwave dynamic therapy (MWDT) for cancer treatment. We found that two AIEgens (TPEPy-I and TPEPy-PF6) served as a new type of microwave (MW) sensitizers to produce ROS, including singlet oxygen (1O2), resulting in efficient destructions of cancer cells. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22 μM, respectively. Overall, the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT, but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome, thus reducing the occurrence of side-effects of MW radiation.
Point-of-care testing for sexually transmitted infections in low-resource settings
Authors: S. Vargas, G. Calvo, J. Qquellon, F. Vasquez, K. Blondeel, R. Ballard, I. Toskin
Journal: Clinical Microbiology and Infection (2021)

Both the global incidence and the prevalence of sexually transmitted infections (STIs) continue to increase, affecting hundreds of millions of individuals, particularly in low-to middle-income countries. Although a definitive diagnosis is desirable to inform STI treatment, syndromic management is the most widely used strategy in resource-limited settings. With the development of point-of-care (POC) tests, it is important to discuss how laboratories will need to adapt to new training and supervisory roles in support of testing, which will largely be performed by peripheral clinical staff.To discuss potential applications of STI POC tests, how they could improve existing STI control strategies and the role of clinical and reference laboratories in support of initiatives to improve STI management and control activities.Narrative literature review and expert opinion.The paper outlines the current status of the STI epidemic worldwide and discusses the problems associated with current approaches to control these infections, particularly in low-resource settings. The roles of clinical and reference laboratories will need to change to provide support for POC and near-patient STI testing as these technologies are introduced into clinical as well as laboratory settings.Laboratories will be expected to play a leading role in the introduction and implementation of POC and near-patient STI testing. They will be required to facilitate training and provide technical and supervisory support to clinical staff on the use of these technologies to augment existing STI management and surveillance programmes. In order to provide quality service, they will need to develop, introduce and maintain sustainable local quality control and external quality assurance systems. Evidence from implementation research for introduction and scale up of STI POC tests in different STI epidemic and laboratory infrastructure settings is required.
Radiotherapy and Immunotherapy Combinations in the Treatment of Patients with Metastatic Disease: Current Status and Future Focus
Authors: William Tyler Turchan, Sean P. Pitroda, Ralph R. Weichselbaum
Journal: Clinical Cancer Research (2021)

Abstract Radiotherapy and immunotherapy benefit subsets of patients with metastatic cancer. Here, we review selected laboratory and clinical studies investigating the utility of combining radiotherapy and immunotherapy in metastatic patients. We examine potential approaches to increase the therapeutic ratio of radioimmunotherapy in the treatment of metastatic cancers moving forward.
Trial in progress: Phase I/II study of radiation therapy followed by intrathecal trastuzumab/pertuzumab in the management of HER2<sup>+</sup> breast leptomeningeal disease.
Authors: Kamran A. Ahmed, Youngchul Kim, Michelle DeJesus, Priya Kumthekar, Nicole Olivia Williams, Joshua David Palmer, Pierre Giglio, Adrienne Ann Boire, John Arrington, Solmaz Sahebjam, Marilin Rosa, Hatem Hussein Soliman, Hsiang-Hsuan Michael Yu, Hyo S. Han, Peter A. J. Forsyth
Journal: Journal of Clinical Oncology (2021)

TPS1099 Background: HER2 + breast cancer patients with leptomeningeal disease (LMD) represent a poor prognosis population with a high unmet clinical need. Although a multitude of treatment options are available for the management of systemic disease, once metastases travel to the leptomeninges, patients have a lack of treatment options aside from traditional local approaches. Data from a phase I/II study reveals intrathecal (IT) trastuzumab to be well tolerated with improved overall survival (OS) compared to historical controls in HER2 + breast LMD. Radiotherapy can improve the flow of IT therapy through the cerebrospinal fluid (CSF) and provide symptomatic relief. The monoclonal antibody pertuzumab is used in conjunction with trastuzumab in the management of metastatic and localized HER2 + breast cancer. Given the role of radiotherapy in the management of LMD along with the role of pertuzumab in the management of HER2 + breast cancer, there is a strong clinical rationale to combine radiotherapy with IT trastuzumab/pertuzumab in the management of HER2 + breast LMD. Methods: The study is designed as a prospective, single-arm, nonrandomized, open-label, phase I/II trial of radiation therapy followed by IT trastuzumab/pertuzumab in the management of HER2 + breast LMD. HER2 + LMD patients identified by magnetic resonance imaging (MRI) and/or CSF cytology, ≥ 18, with a life expectancy &gt; 8 weeks are eligible. Treatment is initiated with radiotherapy, whole brain radiotherapy and/or focal brain/spine radiation followed by IT trastuzumab/pertuzumab. Safety and feasibility will be monitored by a modified toxicity probability interval-2 (mTPI-2) design. Dose reductions of IT trastuzumab will not be allowed. Once the maximum tolerated dose of IT pertuzumab is determined, the phase II portion of the study will commence to determine OS. Secondary objectives involve defining the CSF pharmacokinetics of IT trastuzumab/pertuzumab, evaluating the response rate (leptomeningeal and parenchymal), and progression free survival (leptomeningeal and parenchymal) following IT trastuzumab/pertuzumab. In the phase 2 portion, a single-arm two-stage trial is designed using the Restricted-Kwak-and-Jung’s Method. The primary endpoint is one-year OS. An interim analysis will be performed after 20 patients are enrolled. This study is open with 1 patient enrolled at the time of submission. Clinical trial information: NCT04588545 .
Chemotherapy response score: Validation of a three-tier system to quantify histopathologic response to neoadjuvant chemotherapy in ovarian carcinoma.
Authors: Kari Kubalanza, Teresa Kim, Mingyan Zhang, Joshua Garrett Cohen, Sanaz Memarzadeh, Mae Zakhour, Ritu Salani, Jianyu Rao, Gottfried E. Konecny
Journal: Journal of Clinical Oncology (2021)

e17539 Background: Neoadjuvant chemotherapy (NACT) with interval debulking surgery is considered for patients with advanced-stage ovarian carcinoma (OC) who are not ideal candidates for primary debulking surgery due to advanced age, frailty, poor performance status, comorbidities, or who have disease unlikely to be optimally resected. Moreover, response to NACT may be a suitable surrogate end point for long-term clinical outcome in ovarian cancer. The aim of the present study is to evaluate the utility of a three-tier Chemotherapy Response Score (CRS) and validate whether residual disease or evidence of regression following NACT may provide prognostic information in ovarian cancer. Methods: We conducted a retrospective single-institution study of patients who received NACT with carboplatin and paclitaxel for FIGO stage III/IV ovarian cancer. Response to NACT was graded as no or minimal tumor response (CRS1); appreciable tumor response amid readily identifiable viable tumor (CRS2); or complete/near-complete response with no residual tumor or minimal scattered tumor foci (CRS3) as described previously (Böhm S, et al. J Clin Oncol 33:2457-2463). Multivariate progression free survival (PFS) and overall survival (OS) analyses were performed accounting for age, FIGO stage and BRCA status. Results: Of the 86 patients accrued to date, median age was 65 years, 62% had stage IV disease and 16% had a somatic/germline BRCA mutation. CRS scores 1, 2 and 3 were found in 26 (30%), 43 (50%) and 17 (20%) of cases, respectively, and were associated with PFS (log rank p = 0.002). A high CRS score predicted improved PFS and OS (CRS 2/3 vs 1; median PFS 17.3 vs. 11.8 mo, adjusted hazard ratio (HR), 0.33; 95%CI 0.17-0.62; p &lt; 0.001; median OS 47.9 vs. 38.3 mo, adjusted HR 0.36, 95%CI 0.15-0.88, p = 0.026). Similarly, when comparing CRS 3 with 1/2, the high score predicted improved outcome for PFS but not OS (median PFS 17.3 vs. 14.7 mo, adjusted HR, 0.42; 95%CI 0.19-0.95; p = 0.037; median OS 48.6 vs. 46.5 mo, adjusted HR 0.43, 95%CI 0.14-1.35, p = 0.149). Conclusions: In this study, we validate a simple three-tier chemotherapy response scoring system for assessing histopathologic response of OC to NACT. Residual disease and evidence of complete/near complete regression following NACT provides prognostic information in OC. CRS may serve as a potential surrogate marker for long-term outcome and be a useful alternative intermediate end point in future clinical trials.
Ketone Body Supplementation—A Potential New Approach for Heart Disease
Authors: Jennifer Abbasi
Journal: JAMA (2021)

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A phase I study of AK119, an anti-CD73 monoclonal antibody, in combination with AK104, an anti-PD-1/CTLA-4 bispecific antibody, in patients with advanced or metastatic solid tumors.
Authors: Ben Markman, Amy Hsin-Chieh Hsieh, Jermaine Coward, Matteo S. Carlino, Sophia Frentzas, Xiaoping Jin, Baiyong Li, Zhongmin Maxwell Wang, Kon Yew Kwek, Yu Xia
Journal: Journal of Clinical Oncology (2021)

TPS2675 Background: AK119 is a humanized IgG1 monoclonal antibody (mAb) that selectively binds to and inhibits the ectonucleotidase activity of CD73, a cell surface enzyme that converts adenosine monophosphate (AMP) into adenosine. Adenosine has been shown to facilitate tumor-mediated evasion. CD73 inhibition may therefore reduce adenosine accumulation and promote anti-tumor immunity. AK104 is a recombinant humanized IgG1 bispecific antibody that simultaneously binds to programmed cell death protein 1 (PD-1) and cytotoxic T- lymphocyte-associated antigen protein 4 (CTLA-4). Preliminary data from phase I and II studies suggest that AK104 has encouraging anti-tumor activity in selected tumor types and an improved safety profile compared to the co-administration of anti-PD-1 plus anti-CTLA-4 mAbs. Preclinical studies show that CD73 inhibition synergistically increases the anti-tumor activity of PD-1 and CTLA-4 immune checkpoint inhibitors (ICIs). Published early clinical data suggests that anti-CD73 therapy in combination with ICIs produces improved clinical outcomes. Thus, AK119 plus AK104 is postulated to have synergistically enhanced anti-tumor activity compared to the administration of anti-CD73 monotherapy or ICIs alone. Methods: This is a phase 1a/1b, first-in-human, multicenter, open-label study in patients with advanced solid tumors that are refractory to standard therapies. The primary objective is to assess safety, tolerability and dose limiting toxicity; and to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of AK119 in combination with AK104. Secondary objectives are to evaluate antitumor activity, PK and AK119 immunogenicity. The dose-escalation phase will evaluate 5 dose levels of AK119 (1mg/kg to 40 mg/kg Q2W IV) in combination with 6mg/kg AK104 Q2W IV using a 3+3+3 study design. Eligible pts will receive a single dose of AK119 on C0D1 of a 14-day “lead-in” period. Thereafter, from C1D1 pts will receive AK119 in combination with AK104 on a 28-day cycle, until unacceptable toxicity, confirmed progressive disease, subject withdrawal, or for a maximum of 24 months. The “lead-in” period is only applicable for dose-escalation cohorts. Any dose-escalation cohort not exceeding the MTD may be expanded to a maximum of 18 subjects with selected solid tumor types for further evaluation of safety, PK/ PD, immunogenicity, and preliminary anti-tumor activity. Cohort 1 is currently in progress with the first patient enrolled in January 2021. For the dose-expansion phase, cohorts of pts with advanced/metastatic pancreatic cancer or MSS/pMMR colorectal cancer will be enrolled. Cohorts of other tumor types may be added based on emerging pharmacodynamic and anti-tumor response data. Clinical trial information: NCT04572152.
Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis
Authors: Stéphanie Torrino, Eloise M. Grasset, Stephane Audebert, Ilyes Belhadj, Caroline Lacoux, Meagan Haynes, Sabrina Pisano, Sophie Abélanet, Frederic Brau, Stephen Y. Chan, Bernard Mari, William M. Oldham, Andrew J. Ewald, Thomas Bertero
Journal: Cell Metabolism (2021)