tbuckley/cabot-search huggingface dataset:
Efficacy of targeted therapy in alveolar soft part sarcoma: A systematic review and meta-analysis.
Authors: Na Hyun Kim, Chenyu Sun, Apurwa Prasad, Humaed Mohammed Abdul, Saba Batool, Dhiran Verghese, Kelley Elizabeth Kozma
Journal: Journal of Clinical Oncology (2021)

e23543 Background: Alveolar soft part sarcoma (ASPS) is a rare subtype of soft tissue sarcoma, characterized by a specific unbalanced translocation leading to the fusion of the TFE3 gene on chromosome-X to the ASPSCR1 gene on chromosome-17. Despite its indolent course, ASPS presents a challenge in treatment due to its resistance to conventional anthracycline-based chemotherapy and lack of large scale trial data for this rare sarcoma. This review aimed to assess the efficacy of tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) in metastatic alveolar soft part sarcoma. Methods: A systematic search was performed on Embase and Medline databases for studies that assessed best response of patients with unresectable or metastatic ASPS to TKI and ICI therapy, according to the Response Evaluation Criteria in Solid Tumors (RECIST) edition 1.0 or 1.1. This study followed the Preferred Reporting Items for Systematic Reviews (PRISMA) protocol. Four independent reviewers screened abstracts and extracted the data; any discrepancy was resolved by discussion among reviewers. Pooled objective response rate (ORR) and disease control rate (DCR) were obtained using the Freeman-Tukey double-arcsine transformation using random effects model on STATA software (version. 16.1, StataCorp). Results: 27 articles and abstracts published between 2011 and 2020 were included in the review, resulting in 2 randomized clinical trials (104 participants), 14 single arm prospective trials (214 participants), and 11 retrospective studies (120 patients). Among clinical trials, the pooled ORR and DCR were 18% (95% confidence interval [CI] 8 - 30%; I 2 = 72.25%; p &lt; 0.01) and 87% (95% CI 97 - 93%; I 2 = 43.2%; p = 0.03) respectively. Conclusions: The response rate to targeted therapy in metastatic ASPS is not only clinically meaningful, but also comparable to that of first-line chemotherapy. The majority of patients receiving targeted therapy achieved disease control. Patients who had refractory or progressive disease to one targeted agent demonstrated response to other agents. More randomized trials are warranted to expand treatment options and compare to standard of care regimens.
Progression prediction model for solid tumors with clinical and immunological parameters.
Authors: Aleksei Viktorovich Novik, Dmitrii Viktorovich Girdyuk, Tatyana Leonidovna Nekhaeva, Natalia Viktorovna Emelyanova, Anna Semenova, Gulfiya Midhatovna Teletaeva, Dilorom Khamidovna Latipova, Svetlana Protsenko, Irina Alexandrovna Baldueva
Journal: Journal of Clinical Oncology (2021)

2539 Background: The immune system has well-known relation to tumor progression. Numerous immune-related parameters exist, but only a minor part could be used as biomarkers, especially dynamic ones. We trained a progression prediction model based on clinical features and peripheral immune system assessments. Methods: Patients with immunogenic (melanoma, 295, kidney cancer, 81), non-immunogenic (soft tissue sarcoma, 47, colorectal cancer, 26) and multiple primary tumors (29) with immunologic assessments before treatment (23.5%), on therapy (58.3), and in follow-up after the treatment (18.2%) were randomly divided in 7:3 ratio to the training and test groups. Counts of lymphocytes, T-, B, NK cells, cytotoxic lymphocytes, T-helpers were used as immunologic parameters. Age, sex, disease, stage, therapy, mutational status, last response on treatment, disease and therapy duration, previous treatments were used as clinical ones. The model was trained to predict disease progression in the next three months using “Catboost” gradient boosting. We used ROC AUC to test model performance and Yoden’s index for optimal cutoff calculation. We also studied the influence of model prediction on overall survival (OS) and time to progression (TTP) on the test dataset using the Kaplan-Meyer method and Cox regression. Results: We used 1682 assessments of immune parameters (immune status, IS) done in 354 patients (average 5 per patient) to train the model and 616 IS in 124 patients for validation. All IS of one patient were in the same group. The ROC AUC value of the model was 0.801. The model prediction of progression increased the probability of progressive disease from 37.5 to 62% and decreased the response rate from 37,5% to 8.4% (p = 0.016). The model prediction did not add information over known prognostic factors for OS in the multifactorial model but was an independent prognostic factor for TTP (HR 2.204, p = 0.011). False-positive results separate the group of patients with poor prognosis (OS 16 months, TTP 6 months) among patients with clinical benefit from patients with favorable prognosis (OS 61 months, TTP 18 months, p &lt; 0.001), who had a truly negative model prediction. The possibility of prognosis improvement with therapy change was an essential factor for OS and TTP prediction (р &lt; 0.001). The model was useful in predicting higher OS in patients with disease progression (p = 0.033) and shorter response duration in patients with clinical benefit (р = 0.03). Conclusions: Our progression prediction model provides clinically useful information and can be used for decision making in several clinical situations. Its utility should be tested in a prospective trial.
Abstract 15599: A Systematic Review and Meta-Analysis of Transeptal vs Left Atrial Approach for Mitral Valve Surgery
Authors: Amer Harky, Arish Noshirwani, Dimitrios Pousios, Andrew D Muir
Journal: Circulation (2019)

Objectives: We sought to compare the clinical outcomes of mitral valve surgery through conventional left atriotomy [LA] and transeptal approach [TS] Methods: Electronic database search performed fr...
To Alois Alzheimer, From Auguste Deter
Authors: Rebecca Zaritsky
Journal: Annals of Internal Medicine (2021)

Ad LibitumJune 2021To Alois Alzheimer, From Auguste DeterRebecca ZaritskyRebecca ZaritskyNathan Kline Institute, New Brunswick, New JerseyAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-3816 Audio Reading - "To Alois Alzheimer, From Auguste Deter" Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads "To Alois Alzheimer, From Auguste Deter" by Rebecca Zaritsky Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I cannot rememberif you had loved me.Somebody must have,once—must have held meand stroked my hair.I think I rememberhis hands the most,stained with oil.I remember his shouting,but not his name.You only rememberthe sprouting applauseinside my headwhen you opened me.You see, good sir,I have lost myself,so to say.Where am I?You tell me I amin a castle, of sorts.But I have lost myself.Where might my bed be?Did you love me, sir?I cannot remember,so I will believeanything. Author, Article, and Disclosure InformationAffiliations: Nathan Kline Institute, New Brunswick, New JerseyCurrent Author Address: Rebecca Zaritsky; e-mail, becca.[email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - "To Alois Alzheimer, From Auguste Deter" Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads "To Alois Alzheimer, From Auguste Deter" by Rebecca Zaritsky Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics June 2021Volume 174, Issue 6Page: 843 ePublished: 15 June 2021 Issue Published: June 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Incidence of tozinameran adverse events among the employees of National Cancer Institute.
Authors: Patrik Palacka, Jan Slopovsky, Katarina Zanchetta, Lubos Drgona, Eva Badurikova, Beata Bernadicova, Vladimira Baranova, Juraj Pechan, Michal Mego
Journal: Journal of Clinical Oncology (2021)

e18724 Background: Active immunization seems to be the most effective protection against COVID-19. The objective of this prospective study was to explore the side effects of mRNA vaccine Tozinameran and possible differences in their incidence between different categories of employees at the National Cancer Institute in Bratislava, Slovakia (NCI). Methods: Four hundred and thirteen subjects (89 men) were enrolled into this ongoing prospective study in January, 2021. Median age was 47 years (range 19-79 years). Majority were healthcare professionals (N=306), including nurses (N=125), medical-technical workers (N=89), and physicians (N=42). Presence of side effects was entered by the physicians into electronic data files and their accuracy validated for each subject by an independent investigator. Number of adverse events in the subgroups were compared with log-rank test. Results: At median follow up of 4 weeks, injection site pain (63.0%), pain in the extremity (45.5%), and fatigue (28,6%) belonged among the most common adverse events of Tozinameran. Median number of side effects was 2 (range 0-13). Adverse event incidence was significantly higher in females compare to males (median number 2 vs. 1, P &lt; 0.00001). In a subgroup of healthcare professionals, we found a significantly higher incidence of side effects compared to non-healthcare workers (median number 2 vs. 1, P = 0.00017). Conclusions: In this study, incidence of Tozinameran adverse events was significantly higher in females vs. males and healthcare professionals vs. non-healthcare workers. All side effects were mild and no new safety signals were recognized during follow-up. Key Words: Tozinameran, Active Immunization. COVID-19. Healthcare Professionals. Adverse Events. This study was supported by National Cancer Institute in Bratislava (SK) and OncoReSearch (SK).
Hepatotoxicity reports in the FDA adverse event reporting system database: A comparison of drugs that cause injury via mitochondrial or other mechanisms
Authors: Payal Rana, Michael D. Aleo, Xuerong Wen, Stephen Kogut
Journal: Acta Pharmaceutica Sinica B (2021)

Drug-induced liver injury (DILI) is a leading reason for preclinical safety attrition and post-market drug withdrawals. Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI, especially in idiosyncratic liver injury. This study examined liver injury reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for drugs associated with hepatotoxicity via mitochondrial mechanisms compared with non-mitochondrial mechanisms of toxicity. The frequency of hepatotoxicity was determined at a group level and individual drug level. A reporting odds ratio (ROR) was calculated as the measure of effect. Between the two DILI groups, reports for DILI involving mitochondrial mechanisms of toxicity had a 1.43 (95% CI 1.42-1.45; P < 0.0001) times higher odds compared to drugs associated with non-mitochondrial mechanisms of toxicity. Antineoplastic, antiviral, analgesic, antibiotic, and antimycobacterial drugs were the top five drug classes with the highest ROR values. Although the top 20 drugs with the highest ROR values included drugs with both mitochondrial and non-mitochondrial injury mechanisms, the top four drugs (ROR values > 18: benzbromarone, troglitazone, isoniazid, rifampin) were associated with mitochondrial mechanisms of toxicity. The major demographic influence for DILI risk was also examined. There was a higher mean patient age among reports for drugs that were associated with mitochondrial mechanisms of toxicity [56.1 ± 18.33 (SD)] compared to non-mitochondrial mechanisms [48 ± 19.53 (SD)] (P < 0.0001), suggesting that age may play a role in susceptibility to DILI via mitochondrial mechanisms of toxicity. Univariate logistic regression analysis showed that reports of liver injury were 2.2 (odds ratio: 2.2, 95% CI 2.12-2.26) times more likely to be associated with older patient age, as compared with reports involving patients less than 65 years of age. Compared to males, female patients were 37% less likely (odds ratio: 0.63, 95% CI 0.61-0.64) to be subjects of liver injury reports for drugs associated with mitochondrial toxicity mechanisms. Given the higher proportion of severe liver injury reports among drugs associated with mitochondrial mechanisms of toxicity, it is essential to understand if a drug causes mitochondrial toxicity during preclinical drug development when drug design alternatives, more clinically relevant animal models, and better clinical biomarkers may provide a better translation of drug-induced mitochondrial toxicity risk assessment from animals to humans. Our findings from this study align with mitochondrial mechanisms of toxicity being an important cause of DILI, and this should be further investigated in real-world studies with robust designs.
Myanmar: order to close clinics could be “life threatening” for thousands of people with HIV and TB, says MSF
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Humanitarian agency Medecins Sans Frontieres has been instructed to suspend medical activities in Tanintharyi, Myanmar, in a move that could leave thousands of people with HIV and tuberculosis (TB) without access to treatment.

Myanmar’s healthcare system has been severely disrupted since the military coup began in February 2021.1 The Myanmar military—known as the Tatmadaw and widely criticised over its attacks on Rohingya Muslims—has used increasingly lethal tactics …
ADAM10 Evens Out the Double-Edged Sword of Radiotherapy in Pancreatic Cancer
Authors: Carolina J. Garcia Garcia, Joseph Abi Jaoude, Cullen M. Taniguchi
Journal: Cancer Research (2021)

Abstract Radiotherapy plays an important role in the management of pancreatic ductal adenocarcinoma (PDAC), especially when patients are not surgical candidates. Radiation-induced tumor death provokes an acute inflammation followed by a late-fibrotic response that parallels the fibroinflammatory tumor microenvironment of PDAC, inciting the question of whether radiation-induced fibrosis contributes to PDAC progression. The study published in this issue by Mueller and colleagues presents a potential mechanism linking radiation-induced fibrosis with expression of a disintegrin and metalloprotease 10 (ADAM10) and ephrinB2, which may also contribute to tumor progression. The authors show that ablation of ADAM10 decreases radiation-induced fibrosis and improves survival in preclinical models. These data suggest that targeting ADAM10 may help to improve clinical outcomes with radiotherapy, particularly if definitive radiation is not possible. A better understanding of the biology of radiotherapy in pancreatic cancer remains crucial, and Mueller and colleagues offer important insight in this regard. See related article by Mueller et al., p. 3255
Outcomes of thymic epithelial tumors (TETs) with pleural metastases: Real-world insight from RYTHMIC.
Authors: Jean-Michel Maury, Jose Carlos Benitez, Marie Eve Boucher, Eric Dansin, Mallorie Kerjouan, Laurence Bigay-Game, Eric Pichon, Francois Thillays, Pierre-Emmanuel Falcoz, Lyubimova Svetlana, Youssef Oulkhouir, Calcagno Fabien, Luc Thiberville, Christelle Clément Duchene, Virginie Westeel, Pascale Missy, Pascal Alexandre Thomas, Thierry Molina, Nicolas Girard, Benjamin Besse
Journal: Journal of Clinical Oncology (2021)

8578 Background: TETs are rare and potentially aggressive malignancies with high associated prevalence of autoimmune disorders (AIDs). The pleura is the main metastatic site at relapse, referred as Masaoka-Koga stage (MK) IVa. The benefit of surgical management is unknown, so we have collected outcomes of patients with MK IVa TETs in a large prospective database. Methods: RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French nationwide network mandated to systematically discuss every case of TETs. The database, hosted by IFCT (Intergroupe Francophone de Cancérologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in RYTHMIC national or regional tumor boards. We analyzed epidemiologic, clinical and pathological characteristics of patients (pts) with MK IVa TETs. Results: From January 2012 to December 2019, 2909 pts were included in the database, including 182 MK IVa (6.2%). The median age at diagnosis was 63.5 (range 9 to 91). 58/182 (32%) pts reported AIDs, 76% myasthenia gravis. 129/182 pts had synchronous pleural metastasis. 118/182 (65%) tumors were resected, of them 10 (8.4%) had only pericardial metastases. Thymoma (T) B2 rate was 35.6%, B3 17.8% and thymic carcinoma (TC) 13.5%. Induction chemotherapy (CT) was given in 46 (39%) T and 10 (8%) TC with response rate of 50% and 70% respectively. Thymectomy was performed in addition to pleurectomy in 44 pts (37.2%), pericardiectomy in 68 (57.6%), lung resection in 80 (67.8%) or pneumonectomy in 15 (12.7%). Node resection was performed in 57.6% (n = 67), 12 (18%) were positive. The complete resection rate assessed by surgeons was 57% with a median of 15 (0 to 28) resected pleural metastasis. Intrapleural chemotherapy was added for 19 (16%) pts. No mortality was reported 90 days after surgery procedure. Median follow-up was 36 months. Pleural recurrence was seen in 47 (72%) pts. Median disease-free survival (DFS) was 39 vs 16 months in resected vs not resected tumors (p &lt; 0.0001), 5-years overall survival (OS) was 88 vs 66% (p = 0.28), respectively. Risk of relapse decreased by 60% with surgery (HR = 0.4, 95CI (0.25-0.62); p &lt; 0.0001). Conclusions: The prevalence of MK IVa in our cohort was 6.2%. Surgery appears to be a safe and valid option for pts with MK IVa TET at diagnosis.
Antimetastatic effect of organotin compounds on the model of melanoma B16 in the experiment.
Authors: Margarita Avdeevna Dodokhova, Inga Movlievna Kotieva, Dmitriy Borisovich Shpakovsky, Andrej Vladimirovich Safronenko, Ekaterina Fedorovna Komarova, Margarita Stefanovna Alkhuseyn-Kulyaginova, Elena Rudolfovna Milaeva, Alexander Albertovich Shtil
Journal: Journal of Clinical Oncology (2021)

e21564 Background: Melanoma is an extremely malignant tumor. The unfavorable prognosis in the treatment of patients is mainly due to aggressive metastasis of the tumor in various ways: hematogenic, lymphogenic and lymphohematogenic. Metastatic melanoma cells are relatively drug - resistant. Despite some successes in the treatment of melanoma, the search for new antimetastatic substances remains an urgent task of experimental pharmacology and oncology. Organotin compounds were studied by us as promising candidates for antimetastatic agents. Methods: The study was conducted on experimental C57BL/6 mice (n =72, each cohort contained 12 mice) with B16 melanoma (subcutaneous transplantation) to determine the intensity of metastasis in the presence of the cytotoxic organotin compound dimethyltin bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) [1-3] (Me3). All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Female mice (8 weeks of age, weighing 21-22 g) were administered intraperitoneal 1% aqueous gelatin solution of organotin Me3 daily for 5 days. The total doses in the first series of the experiment were 150, 250, 375 mg/kg (I, II, III cohorts and IV control group), which allowed us to choose the most effective dose of Me3. After that, in the second series of experiments, the metastasis inhibition index was evaluated in group V (total dose 375 mg/kg) and control group VI. The animals were euthanized on the 18th day after the tumor was inoculated. Results: It was shown that when administered intraperitoneal to mice, Me3 did not inhibit the growth of B16 melanoma in any of the groups. The results showed that the average life expectancy of animals in the experimental group III with the introduction of Me3 at a dose of 375 mg/kg significantly increased and amounted to 30.1±2.5 days, in control mice of group IV-21.8±2.6 days. In the second series of the experiment, after 18 days, the index of metastasis inhibition was almost twice lower (54%) in group V than in the control group (VI). Conclusions: It is concluded that the overall result of this study clearly demonstrates that the organotin compound dimethyltin bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) (Me3) is an effective antimetastatic agent in transplanted experimental mouse melanoma B16 at a total dose of 375 mg/kg.
Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients
Authors: Gwen M H E Dackus, Katarzyna Jóźwiak, Gabe S Sonke, Elsken van der Wall, Paul J van Diest, Sabine Siesling, Michael Hauptmann, Sabine C Linn
Journal: JNCI Journal of the National Cancer Institute (2021)

The benefit of adjuvant aromatase inhibitors (AI) vs tamoxifen has been investigated in randomized clinical trials for premenopausal and postmenopausal patients with early, estrogen receptor-positive (ER+) breast cancer. The optimal endocrine treatment for chemotherapy-treated perimenopausal women, who generally develop chemotherapy-induced amenorrhea, is uncertain.All Dutch women who received adjuvant chemotherapy and endocrine treatment for stage I-III, ER+ (>10% positive cells), invasive breast cancer diagnosed between 2004 and 2007 were identified through the Netherlands Cancer Registry. Included women were considered perimenopausal based on an age at diagnosis of 45 to 50 years (n = 2295). For each patient, AI treatment duration relative to total endocrine treatment duration was calculated. Predominantly tamoxifen-treated patients (AI < 25%) were compared with those receiving AI and tamoxifen for a similar duration (AI 25%-75%) and those mostly using AI (AI > 75%). Adjusted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival were calculated using time-dependent Cox regression.After an average follow-up of 7.6 years, 377 RFS events occurred. Women mostly receiving AI (AI > 75%) had the best RFS (adjusted HR = 0.63, 95% confidence interval = 0.46 to 0.86) followed by those receiving AI 25% to 75% (adjusted HR = 0.85, 95% confidence interval = 0.65 to 1.12) compared with predominantly tamoxifen-treated women. Trend analyses showed that every 10% increase in AI-endocrine treatment ratio reduced RFS event risk by 5% (2-sided Ptrend = .002). In total, 236 deaths occurred; hazard ratios for overall survival showed similar trends.These results suggest that the best adjuvant endocrine treatment for chemotherapy-treated, ER+ breast cancer patients diagnosed aged 45-50 years consists of mainly AI followed by a switch strategy and mainly tamoxifen.