tbuckley/cabot-search huggingface dataset:
Characterization of NTRK gene fusion events in solid tumors among Chinese patients.
Authors: Xuhui Zhang, Dongsheng Chen, Qin Zhang, Qianqian Duan, Qing WANG, Si Li, Mingzhe Xiao
Journal: Journal of Clinical Oncology (2021)

e15040 Background: NTRK fusions are actionable genomic alterations detected across tumor types. NTRK gene fusions involving either NTRK1, NTRK2 or NTRK3 (encoding the neurotrophin receptors TRKA, TRKB and TRKC, respectively) are oncogenic drivers of various adult and paediatric tumour types. Here, we update the detection of NTRK gene fusions across tumor types and further describe fusion partner characteristics among Chinese patients. Methods: Samples submitted for clinical molecular profiling were retrospectively analyzed for NTRK fusion events. Method for identifying NTRK fusions was DNA-based next-generation sequencing that tumour DNA is extracted from formalin-fixed paraffin-embedded tissue. All NTRK fusion partners were identified for intact functional domains, domain prediction, breakpoints, frame retention and co-occurring alterations. Results: A total of 64 NTRK fusion events (0.26% of 24,451) were identified. NTRK fusions are characteristic in a few rare types of cancer, such as melanoma, glioma and carcinomas of the thyroid, lung and colon, but they are also infrequently seen in some uncommon cancers, such as secretory carcinoma of the breast or salivary gland and infantile fibrosarcoma. Among the fusions, NTRK1 (0.08% of 24,430), NTRK2 (0.02% of 24,445), NTRK3 (0.15% of 24,414) were identified. Twenty-six unique fusion partners were identified, the most common in NTRK1 fusion being TPM3 (23.8%), NTRK2 fusion being AGTPBP1 (33.3%), and NTRK3 fusion being TFG (13.5%). Almost 53.8 % (14 of 26) of all fusion events are expected to include the transmembrane domain contributed by the NTRK fusion partner. The most commonly identified breakpoints occur in exon 14 and exon 17 and in exon 15 and exon 20, in NTRK1, NTRK3, respectively. Conclusions: NTRK fusion products are diverse across tumor types, but the significance of these variations is not clear. The biological and clinical implications of retaining certain domains of NTRK and of fusion partners warrants further investigation.
How kindness can be contagious in healthcare
Authors: Weiming Tang, Dan Wu, Fan Yang, Cheng Wang, Wenfeng Gong, Kurt Gray, Joseph D. Tucker
Journal: Nature Medicine (2021)

Pay-it-forward programs, whereby someone receives a gift or free service and then gives a gift to another person in return, have expanded during the COVID-19 pandemic and provide an opportunity for healthcare providers to reduce costs, increase uptake of interventions such as testing and vaccines, and promote sustainability.
Anlotinib in combination with TQB2450 in patients with recurrent ovarian cancer (ACTION): A multicenter, single-arm, open-label, phase Ib trial.
Authors: Chunyan Lan, Jing Zhao, Fan Yang, Rong Li, Yu Huang, Jing Wang, Weihong Zhao, Li Zhang, Chang Liu, Xuehan Bi, Haihong Jin, Jin Meng, Xin Huang
Journal: Journal of Clinical Oncology (2021)

5557 Background: Combination of antiangiogenic therapy and immune checkpoint inhibitor therapy is reported as an effective antitumor strategy. TQB2450 is a humanized IgG1 monoclonal antibody against programmed death-ligand 1 (PD-L1). We aimed to assess the activity and safety of TQB2450 plus the antiangiogenic multi-target tyrosine kinase inhibitor anlotinib in patients with recurrent advanced ovarian cancer. Methods: The study with ClinicalTrials.gov identifier NCT04236362 is an open-label, multicohort, and multicenter phase Ib trial evaluating the efficacy and safety of anlotinib combined with TQB2450 in patients with advanced gynecologic cancer. The present study (ACTION study) reports the ovarian cancer cohort. We enrolled patients aged 18–70 years with platinum-resistant or platinum-refractory epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST). Eligible patients received anlotinib 12 mg per day orally on days 1 to 14 and TQB2450 1200 mg intravenously on day 1, every three weeks. Treatment continued until disease progression, unacceptable toxicity, and withdrawal of consent. The primary endpoint was objective response rate (ORR) assessed by investigators according to RECIST version 1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DOR), overall survival (OS) and safety. Results: Between 21 Feb 2020 and 15 Jan 2021, 33 patients with a median age of 55 years (range, 26-71) were enrolled and received study treatment. Patients had received at least once platinum-based chemotherapy, and the median number of previous chemotherapy lines was 3 (range, 1–6). 30.3% patients had bevacizumab therapy before enrollment. At data cutoff (15 Jan 2021), the median follow-up was 5.1 months (range, 0.1–10.8). In the 25 efficacy-evaluable patients, 13 of them achieved partial response, yielding the ORR of 52.0% (95% CI, 30.4%–71.6%). The median PFS was 6.7 months (95% CI, 4.5 months to not reached). The median duration of response and the median OS were not reached. The treatment-related grade 3 or 4 adverse events (AEs) occurred in 54.5% patients, and the most common ones were palmar-plantar erythrodysesthesia syndrome (21.2%) and hypertension (18.2%). The most potential immune-related AEs included grade 1 to 2 hypothyroidism (24.2%) and fatigue (9.1%). No treatment-related death was recorded. Conclusions: Anlotinib plus TQB2450 showed encouraging antitumor activity and tolerable toxicity in patients with recurrent advanced ovarian cancer. Clinical trial information: NCT04236362.
Infographic. Benefits and harms of exercise therapy in people with multimorbidity
Authors: Alessio Bricca, Lasse Kindler Harris, Madalina Jäger, Susan Smith, Carsten B Juhl, Søren T Skou
Journal: British Journal of Sports Medicine (2021)

People with multimorbidity (two or more medical conditions) have poorer physical and psychosocial health and higher risk of hospital admission and premature death.1 The complexity and increased burden of multimorbidity presents challenges for healthcare systems.2 Therefore, the current standard of care for patients with multimorbidity includes visiting many healthcare professionals and reviewing different pharmacological treatments with inherent risk of side effects. This is often unsatisfactory for the patients.3 

Exercise is considered a core treatment for at least 26 chronic conditions. However, little is known about its effects in people with multimorbidity. To fill this gap, we performed a systematic review of randomised controlled trials to investigate the benefits and harms of exercise therapy (ie, a regimen or plan of physical activities designed and prescribed …
Pensions: government policy has affected the NHS workforce, say MPs
Authors: Abi Rimmer
Journal: BMJ (2021)

NHS pensions rules led to doctors reducing their working hours or retiring early, MPs have concluded.

The Commons Public Accounts Committee’s review of public sector pensions1 found that pensions affect employees’ decisions about their work and that NHS Pension Scheme rules had led to a large number of doctors reducing their working hours, opting out of the scheme, or retiring early.

“It is becoming clear that public service pension policy is affecting the delivery of frontline services in some areas, such as education and health,” the report said.

MPs said that the Treasury should regularly …
AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction
Authors: Rabea Hinkel, Sandor Batkai, Andrea Bähr, Tarik Bozoglu, Sarah Straub, Tobias Borchert, Janika Viereck, Andrea Howe, Nadja Hornaschewitz, Lisa Oberberger, Victoria Jurisch, Rainer Kozlik-Feldmann, Franz Freudenthal, Tilman Ziegler, Christian Weber, Markus Sperandio, Stefan Engelhardt, Karl Ludwig Laugwitz, Alessandra Moretti, Nik Klymiuk, Thomas Thum, Christian Kupatt
Journal: Journal of the American College of Cardiology (2021)

Pathological cardiac hypertrophy is a result of afterload-increasing pathologies including untreated hypertension and aortic stenosis. It features progressive adverse cardiac remodeling, myocardial dysfunction, capillary rarefaction, and interstitial fibrosis often leading to heart failure. This study aimed to establish a novel porcine model of pressure-overload–induced heart failure and to determine the effect of inhibition of microribonucleic acid 132 (miR-132) on heart failure development in this model. This study developed a novel porcine model of percutaneous aortic constriction by implantation of a percutaneous reduction stent in the thoracic aorta, inducing progressive remodeling at day 56 (d56) after pressure-overload induction. In this study, an antisense oligonucleotide specifically inhibiting miR-132 (antimiR-132), was regionally applied via intracoronary injection at d0 (percutaneous transverse aortic constriction induction) and d28. At d56, antimiR-132 treatment diminished cardiomyocyte cross-sectional area (188.9 ± 2.8 vs. 258.4 ± 9.0 μm2 in untreated hypertrophic hearts) and improved global cardiac function (ejection fraction 48.9 ± 1.0% vs. 36.1 ± 1.7% in control hearts). Moreover, at d56 antimiR-132-treated hearts displayed less increase of interstitial fibrosis compared with sham-operated hearts (Δsham 1.8 ± 0.5%) than control hearts (Δsham 10.8 ± 0.6%). Of note, cardiac platelet and endothelial cell adhesion molecule 1+ capillary density was higher in the antimiR-132–treated hearts (647 ± 20 cells/mm2) compared with in the control group (485 ± 23 cells/mm2). The inhibition of miR-132 is a valid strategy in prevention of heart failure progression in hypertrophic heart disease and may be developed as a treatment for heart failure of nonischemic origin.
COVID-19 disease in patients with LUNG cancer in Spain: GRAVID LunG canceR pAtients coVid19 Disease (GRAVID STUDY).
Authors: Mariano Provencio, Jose Maria Mazarico, Antonio Calles, Monica Antoñanzas, Cristina Pangua, Xabier Mielgo, Ernest Nadal, Rafael Lopez Castro, Ana López Martín, Edel del Barco, Manuel Domine, Virginia Calvo, Pilar Diz, Carmen Sandoval García, Elia Sais, Ivana Sullivan, Maria Angeles Sala, Gema García Ledo, Javier Baena Espinar, Maria Gonzalez Cao
Journal: Journal of Clinical Oncology (2021)

e18709 Background: Patients with cancer may be more susceptible to infection and at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The LunG canceR pAtients coVid19 Disease (GRAVID) study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19. Methods: In this large nationwide study, we reviewed medical records of patients with lung cancer and confirmed COVID-19 diagnosis from 65 Spanish hospitals. Clinical features, treatments and disease outcomes were collected. The primary endpoint was to determine all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU). Risk factors for poor prognosis were identified by univariate and multivariate logistic regression models. Results: Overall, 447 patients were included for analysis. Mean age was 67·1 ± 9·8 years; 332 (74·3%) were men, and 383 (85·7%) current/former smokers. NSCLC was the most frequent type of cancer (377, 84·5%), consisting mainly of adenocarcinoma (228, 51·0%), and stage III metastatic or unresectable disease (354, 79·2%). Two-hundred and sixty-six (59·5%) patients were receiving anticancer treatment, mostly first-line chemotherapy. In total, 350 (78·3%) patients were hospitalized for a mean of 13·4 ± 11·4 days, nine (2·0%) patients were admitted to the ICU, and 146 (32·7%) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates. Conclusions: Due to their underlying comorbidities and immunocompromised status, patients with lung cancer and COVID-19 show high hospitalization and mortality rates. These outcomes, alongside the identification of prognostic factors, may inform physicians on the risks and benefits in this population, in order to provide individualized oncological care.
Optimizing blood product utilization: A whole lot to gain and nothing to lose!
Authors: Adam F Binder, Katy Loos, Alexis Peedin, Julie Karp, Usama Gergis, Lindsay Wilde
Journal: Journal of Clinical Oncology (2021)

e18669 Background: Transfusion stewardship is a vital part of managing patients with hematologic malignancies (HM). Blood products are limited resources and blood product transfusion (txn) is costly and poses complications. Randomized trials in different clinical settings have shown that a conservative txn strategy is not inferior to more liberal txn strategy. As a result, the AABB and ASCO have recommended following a conservative txn strategy in patients with cancer (hemoglobin (hg) &lt;7-8g/dL and platelets (plt) &lt;10K in stable non-bleeding patients). Here we report our early outpatient institution’s experience implementing a contemporary txn approach in patients with HM. Methods: We formed a multi-disciplinary team to analyze blood product utilization. Overutilization was defined as orders for multi-units, packed red blood cells (pRBC) for hg &gt;8 or plt for plt &gt;10K in stable non-bleeding patients. Patients’ charts were audited during the baseline period to understand practice patterns. Data were collected using Qlik database. The baseline period (May 1, 2019-Feb 29, 2020) was compared to the intervention period (March 1 – December 31, 2020). A root cause analysis was performed. When possible 2-sided paired T-test was performed. If not possible, descriptive statistics were performed. Three interventions were developed and implemented sequentially: March 2020 – Blood bank began real-time review of blood products overutilization. May 2020 – Electronic Medical Record txn order set was revised to reflect recommended best practices. October 2020 –Txn guidelines revised for patients with HM. Results: During the study period, there were 3,227 pRBC and 2,817 plt transfused units in the outpatient setting. Monthly pRBC txn decreased from (mean(SD)) 168.5 (16.6) to 154.2(16.4) (p value: 0.14). Monthly plt txn decreased from 166.5 (26.5) to 115.2 (26.2) (p value: 0.001). Rates of multi-unit orders decreased significantly. Average monthly multi-unit orders decreased for pRBC (pre-48.6(5.9);post-24.3(7.6);p value 0.00007) and plts (pre-67.4(11.8);post-21.3(23.3);p value: 0.0002). Average hb at time of txn in the pre- and post-intervention period was 7.47 and 7.22. The percentage of txn in which the indication for txn was hb &lt;7, 7-8, &gt;8 changed from 34.6% to 56.3%, 52.6% to 32.8%, and 12.8% to 10.9% respectively. There was no significant increase in admissions for bleeding or increase in number of outpatient visits during the study period. Conclusions: Over 10-months, we significantly reduced outpatient blood product. Robust quality improvement methodology, engaging key stakeholders, and changing the culture of outpatient management were keys to success. To date, we have not seen any unintended consequences of these changes. These results are encouraging, as outpatient transfusion stewardship is thought to be harder given concerns about patients not being monitored as closely as in the inpatient setting.
Predicting symptom complexity: Using autoregressive integrated moving average (ARIMA) models to create responsive clinic scheduling.
Authors: Linda Watson, Siwei Qi, Andrea Deiure, Claire Link, April Hildebrand, Lindsi Chmielewski, Louise Smith, Dean Ruether, Krista Rawson
Journal: Journal of Clinical Oncology (2021)

e13529 Background: Increasing cancer incidence, coupled with a trend in treating patients for longer periods of time, presents challenges in addressing all patients’ symptoms/concerns within the allotted time for ambulatory clinic appointments. Consequently, the ability to forecast and monitor the percentage of cancer patients with different symptom complexity levels is extremely valuable. Symptom complexity is a summary score that weighs the severity of all patient reported symptom scores at one time point. If a clinic could predict how many patients may need more time due to complex symptom management needs, clinic-scheduling templates could be adjusted to include a set number of longer appointments. Methods: Auto Regressive Integrated Moving Average (ARIMA) models were utilized to forecast the percentage of patients with a high symptom complexity level within one cancer clinic in Alberta, Canada. Goodness-of-fit measures such as Bayesian information criterion (BIC) and Ljung-Box test were used to determine optimal form for the ARIMA model. Following model selection, the autocorrelation function (ACF) was performed. These tests together verified that chosen AR, MA and differencing (I) were appropriate. Model performance on the historical data for model fit was summarized by Mean Absolute Error (MAE) and Root Squared Mean Error (RSME). Forecasting accuracy was assessed using mean absolute prediction error by comparing the forecasts with actual clinic data. Results: Of the multiple model structures tested, ARIMA (0, 0, 1) was selected, with the lowest BIC and non-significant Ljung-Box test. We obtained forecasts of the percentage of patients with high symptom complexity levels, with an MAE at 4.0%. To assess forecast accuracy, we calculated the absolute prediction error by comparing the forecasted percentages of patients with high symptom complexity levels to actual clinic visit data and the mean absolute prediction error was 5.9%. Conclusions: This forecasting model has important implications, allowing clinics to adjust scheduling templates to provide a select number of longer timeslots and therefore, be better prepared to meet the symptom management needs of cancer patients who are considered highly complex. This model could be applied to other clinical populations to allow for a tailored scheduling approach based on each clinic’s symptom complexity forecasting.
TGF-β and PD-L1 inhibition combined with definitive chemoradiotherapy in esophageal squamous cell carcinoma: A phase II clinical trial (NCT04595149).
Authors: Linde Veen, Maarten C.C.M. Hulshof, Connie R. Jimenez, Edwin P.J.G. Cuppen, Laurens V. Beerepoot, Geert-Jan Creemers, W. Edward Fiets, Paul M. Jeene, Djoeri Lipman, Nadia Haj Mohammad, Vera Oppedijk, Marije Slingerland, Walter L. Vervenne, Maarten F. Bijlsma, Hanneke W.M. Van Laarhoven
Journal: Journal of Clinical Oncology (2021)

TPS4154 Background: Esophageal cancer is the 6th leading cause of mortality worldwide, with an overall 5-year survival rate of 10%. This is in part due to more than 50% of patients presenting with irresectable or metastatic disease. With the introduction of definitive chemoradiation, 3-year survival rates of patients with irresectable tumors have risen to up to 40% (Hulshof et al., ASCO GI Oral Presentation, 2020). However, treatment still fails in the majority of patients due to locoregional recurrences or development of metastatic disease. Recently, it has been shown that addition of TGF-β inhibition to chemoradiation may improve treatment efficacy (Steins et al., Int J Cancer, 2019). Additionally, PD-L1 inhibition has emerged as a relevant therapeutic strategy in specific patient subgroups, such as squamous cell carcinoma (Kato et al., The Lancet Oncology, 2019). In this phase II study, we will investigate the feasibility of addition of bintrafusp alfa, a bifunctional fusion protein blocking TGF-β and PD-L1, to definitive chemoradiation in patients with esophageal squamous cell carcinoma. Methods: To assess feasibility, 52 patients will receive definitive chemoradiation combined with three doses of bintrafusp alfa at week 1, 4 and 7 (Table). Feasibility is defined as ≥80% of patients completing 2 cycles of bintrafusp alfa and will be tested with a one-sample test for a binomial proportion, comparing the observed percentage to the fixed reference value of unfeasibility (62%). Secondary endpoints are toxicity, progression-free survival, overall survival and quality of life. Additionally, exploratory endpoints include development of biomarkers to predict treatment response. Eligible for inclusion are patients with surgically irresectable (T1-4a N+ M0) squamous cell carcinoma of the esophagus or gastro-esophageal junction, or patients with resectable tumors refraining from radical surgery. Patients with M1 disease solely on the basis of supraclavicular metastasis are eligible. Patients with locoregional recurrences are eligible, provided that full dose of radiation can be safely delivered. Currently, 2 of planned 52 patients have been enrolled. Clinical trial information: NCT04595149. [Table: see text]
Long-term follow-up outcomes and treatment among patients previously treated with Zizao Yangrong granules (ZYG) for egfris–related skin xerosis.
Authors: Chongxiang Xue, Jia Li, Xingyu Lu, Huijuan Cui
Journal: Journal of Clinical Oncology (2021)

e24054 Background: Traditional Chinese medicine (TCM) has broad prospects in the treatment of targeted drugs–related dermatologic toxicity. In our previous study (ChiCTRIOR-17013498), Zizao Yangrong granules (ZYG) made effect on EGFRIs-related xerosis and improve the quality of life. However, some people still doubt that TCM could affect therapeutic benefit for patients treated with EGFRIs. Methods: Patients with EGFRIs related xerosis who underwent ZYG and vitamin E ointment from May 2016 to January 2018 were retrospectively reviewed. Survival data and quality of life data analysis were performed. Besides, patients who used ZYG for more than 8 weeks were also summarized, followed by telephone follow-up and questionnaire survey. Results: Of 68 participates randomly assigned, 54 patients were successfully followed up. Median PFS in Vitamin E Ointment plus ZYG group was 41.6 months, and that in Vitamin E Ointment group was 40.9 months, with no statistical difference (HR 0.85, 95% CI 0.48 to 1.51, P = 0.586). Subsequently, 19 patients who used ZYG for longer than 8 weeks were also included. 2 patients reported complete response, 14 patients reported partial response, and 3 patients reported no response. The overall effective rate was 84.2%. The total DLQI score of patients with long-term intervention of ZYG was 4.47±3.10. Compared with baseline DLQI score (7.00±2.91), the DLQI of patients after ZYG intervention has been significantly improved (P = 0.000). During the continuous use of ZYG treatment, incidence of adverse effects was 57.9%. Treatment-related adverse reactions were mostly mild, with no grade 3/4 adverse events. Conclusions: ZYG did not affect progression free survival of patients treated with EGFRIs. And long time-scale ZYG intervention could continuously relieve EGFRI-related xerosis and significantly improve the quality of life of patients without serious adverse effects. Clinical trial information: ChiCTRIOR-17013498.