tbuckley/cabot-search huggingface dataset:
Survival in 31 670 patients with thin melanomas: a Swedish population‐based study*
Authors: K. Isaksson, R. Mikiver, H. Eriksson, J. Lapins, K. Nielsen, C. Ingvar, J. Lyth
Journal: British Journal of Dermatology (2020)

The incidence of cutaneous malignant melanoma (CMM) continues to increase in most countries worldwide and the majority are diagnosed with thin tumours (≤ 1 mm).The aim of the present study was to investigate the melanoma-specific survival (MSS) as well as conditional MSS (CMSS) in patients with thin CMM in Sweden.Clinical and histological parameters were obtained from the Swedish Melanoma Registry for patients diagnosed with thin CMM between 1990 and 2017. Patients were followed until the end of 2017. MSS as well as CMSS for different thickness groups were calculated using the Kaplan-Meier method and Cox regression analyses were used to calculate for survival differences between thickness groups.There were 31 670 patients included for final analyses. The overall 10- and 20-year MSS for thin CMMs was 97% [95% confidence interval (CI) 97-97] and 95% (95% CI 95-96), respectively. From 0·7 mm and above, MSS decreased significantly with increasing thickness level. All thickness groups had an increased survival over time. The lowest CMSS was confirmed for men with 1·0 mm in thickness but their 10-year CMSS increased steadily over time. Women had overall better MSS as well as CMSS than men. However, the relation between MSS and CMSS was similar for both sexes.MSS was confirmed as excellent for patients with thin CMMs in Sweden. Although we could show a decreased MSS for patients with 0·7 mm thickness and above, the long-term survival and, in addition, a very favourable CMSS for those patients do not support more extended follow-up programmes than the current recommendations in Sweden.
Iatrogenic immunosuppression in patients with newly diagnosed high-grade gliomas
Authors: S. A. Grossman, S. Desideri, X. Ye, K. Szajna, M. Chamberlain, G. Lesser
Journal: Journal of Clinical Oncology (2007)

2012 Background: Vaccines and other immunologic interventions hold promise for patients (pts) with high grade gliomas (HGG). However, a prior report noted that CD4 counts dropped significantly during the 6 weeks of radiation (RT) in patients receiving only RT and dexamethasone (Dex). This is the first study to follow CD4 counts in HGG treated with RT, Dex, and temozolomide (TMZ) and to obtain serial CD4 counts for 12 months. Methods: 70 pts with newly diagnosed HGG were accrued before they started RT and TMZ. CD4 counts were obtained before therapy and monthly thereafter for one year. Information on hospitalizations, infections, steroid doses, and survival is also being collected. Descriptive statistics were used. Results: Data is available on 60 pts: 54% are female and 97% are Caucasian. The median age of the pts was 57 (range 30–77) and 78% had a diagnosis of glioblastoma. The median CD4 count before RT was 640 (range 145–1445) which fell to 363 (32–1055), 272 (8–558), and 250 (44–845) in 1, 2, and 3 months respectively. The median CD4 counts during months 4, 6, 8, 10 and 12 were 373, 319, 329, 395, and 269. CD4 counts &lt;200 were recorded in 34 pts (57%) and CD4 &lt;100 in 13 pts (22%) during the study period. Conclusions: This study demonstrates that CD4 counts: 1) are relatively normal prior to radiation, 2) nadir to a median of 250 during the first three months of therapy, and 3) generally remain depressed following the completion of radiation. Severe iatrogenic immunosuppression as evident by CD4 counts is common in this population. Correlations with outcome and steroid doses are underway. These findings have implications for the recommended duration of PCP prophylaxis, the optimal design for therapeutic interventions that require a relatively intact immune system, and studies seeking to increase the intensity or duration of TMZ. No significant financial relationships to disclose.
Prophylaxis of chemotherapy-induced neutropenia: Patterns of care in U.S. community oncology practices
Authors: A. Naeim, L. Friedman, D. J. Pasta, E. P. Elkin, J. Malin, H. Viswanathan, H. Ozer
Journal: Journal of Clinical Oncology (2007)

9123 Background: Adherence to neutropenia guidelines may improve patient outcomes and decrease costs associated with febrile neutropenia (FN). This analysis presents baseline data on patterns of colony-stimulating factor (CSF) use among community-based oncology practices prior to an educational intervention targeted to health care providers to improve adherence to CSF guidelines from the National Oncology Alliance (NOA). Methods: Medical records were identified from 47 participating sites. Abstractors collected data from a sequential sample of adult cancer patients receiving chemotherapy during the year prior to site randomization to an educational intervention (June and August 2006). A complex algorithm was developed to identify patients for whom the NOA guidelines recommend primary prophylaxis with a CSF including (1) patients receiving a chemotherapy regimen with a &gt;20% expected risk of FN and (2) patients receiving chemotherapy with a 10–20% risk of FN and who have one of the following risk factors present: diminished performance status or non-Hodgkin's lymphoma with low serum albumin or high serum LDH or spread to bone marrow. Results: 2594 patients were evaluated for this analysis. Most were female (66%) and the mean age was 61.7 years (± 13.1). During this period (2005–06), 423 (16%) patients received chemotherapy regimens with an FN risk &gt;20% and 143 (6%) received chemotherapy regimens with an FN risk of 10–20% and had a risk factor. Of patients receiving chemotherapy with a &gt;20% risk of FN, 176 (42%) received CSF primary prophylaxis. Of patients receiving chemotherapy with a 10–20% risk FN with a risk factor present, 40 (28%) received CSF primary prophylaxis. Conclusions: Many patients for whom guidelines recommend treatment did not receive CSF primary prophylaxis. After the year-long educational intervention, we will re-evaluate CSF patterns of care and assess whether adherence to guidelines improved patient outcomes. No significant financial relationships to disclose.
A disclosure form for work submitted to medical journals: a proposal from the International Committee of Medical Journal Editors
Authors: Darren B Taichman, Joyce Backus, Christopher Baethge, Howard Bauchner, Annette Flanagin, Fernando Florenzano, Frank A Frizelle, Fiona Godlee, Laragh Gollogly, Abraham Haileamlak, Sung-Tae Hong, Richard Horton, Astrid James, Christine Laine, Pamela W Miller, Anja Pinborg, Eric J Rubin, Peush Sahni
Journal: The Lancet (2020)
Abstract P256: Better Mid-life Life’S Simple 7 Status is Associated With Lower Risk of Recurrent Cardiovascular Disease and All-cause Mortality After Stroke: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yvonne Commodore-Mensah, Yejin Mok, Kunihiro Matsushita, Anna Kucharska-newton, Rebecca F Gottesman, Priya Palta, Wayne Rosamond, Josef Coresh, Silvia Koton
Journal: Circulation (2020)

Introduction: Cardiovascular disease (CVD), including stroke, is a leading cause of morbidity and mortality. Ideal levels of the American Heart Association’s Life’s Simple 7 (LS7) metric are associated with lower stroke risk. However, the association between LS7 and recurrent CVD and mortality after incident stroke is unclear. Hypothesis: Stroke survivors with higher LS7 scores before incident stroke would have lower risk of recurrent CVD and mortality than those with lower scores. Methods: From 14715 individuals free of stroke at ARIC baseline (1987-1989), we analyzed data on 1380 participants who had an incident stroke between 1987-2017. A summary baseline LS7 score (range: 0-14) was derived by assigning 2 points for ideal, 1 point for intermediate, and 0 points for poor on each of the following: smoking, adiposity, physical activity, diet, total cholesterol, blood pressure and fasting glucose at baseline. We calculated adjusted hazard ratios (HR) for a composite and individual CVD outcomes of recurrent stroke, myocardial infarction, heart failure, and all-cause mortality after incident stroke, per a priori categories in baseline LS7 score. Results: At baseline, the mean age of participants with incident stroke was 55.7 ± 5.6 years (53% women, 36% black). Participants with the highest LS7 scores (≥10, n= 3287) had 66% lower risk (HR: 0.34, 95% CI: 0.29-0.40) of incident stroke than those with intermediate cardiovascular (CV) health (4-6, n=4166) ( Table ). During a median (SE) follow-up of 7.5 (0.45) years, 42.5% (587/1380) had recurrent composite CVD after incident stroke. LS7 score at baseline (before incident stroke) was inversely associated with recurrent CV outcomes (composite, myocardial infarction, heart failure) and all-cause mortality after incident stroke but not recurrent stroke (Table) . Conclusions: Better CV health in mid-life before incident stroke was associated with lower risk of recurrent CVD after stroke, suggesting that good CV health is essential for secondary prevention among stroke patients.
Prevalence and temporal patterns of persistence of symptoms in 165 rectal cancer patients receiving preoperative chemoradiation therapy
Authors: S. Krishnan, T. Mendoza, Y. Zhang, X. S. Wang, P. Das, M. E. Delclos, C. Crane, C. Cleeland, N. Janjan
Journal: Journal of Clinical Oncology (2007)

19580 Background: The symptom burden during preoperative chemoradiation therapy for rectal cancer (CRT) has not been objectively characterized previously. The severity and temporal patterns of patient self-reported symptoms during CRT were assessed using the MD Anderson Symptom Inventory (MDASI). Methods: 165 consecutive patients with T3/T4/N+ rectal cancer received 45–55 Gy in 25–30 fractions concurrently with capecitabine chemotherapy. No additional intervention beyond standard supportive care was triggered by the MDASI score severity. The mean symptom scores were grouped into three time points; weeks 0–1 (“baseline”), 2–3 (“early treatment”), and 4–6 (“late treatment”) of CRT. Lowess curves were used to demonstrate the severity and pattern of individual symptoms. Linear mixed models were used to assess changes in symptom severity. Repeated measures analyses compared the mean severity of the reported symptoms at the three time points. Results: The median number of data points per patient was 3.0 (range, 1–6), for a total of 533 data points. Lowess curves demonstrated increasing symptom severity during CRT, which was confirmed by the linear mixed models analysis for each symptom (p&lt;0.05). Using repeated measures with the three time points, these symptoms, except fatigue, showed statistically significant differences in mean severity ( Table 1 ). High baseline fatigue levels blunted statistical power to detect differences during CRT. Despite normal hemoglobin levels, fatigue remained the most severe symptom. Placed in context, the mean symptom levels remained mild throughout CRT. Conclusions: CRT was associated with a high prevalence of and progressive increase in symptom burden during therapy although the functional impact was limited. All symptoms followed clinically recognized patterns. The linear mixed model, a more sensitive measure of these trends, is recommended for prospective studies of interventions for symptom control [Table: see text] No significant financial relationships to disclose.
Can ERCC1 and topoisomerase II-alpha predict histological response and outcome after induction chemotherapy in locally advanced soft tissue sarcomas (LASTS)?
Authors: R. Ruiz-Soto, N. Auger, M. Castaing, F. Drusch, S. Bonvalot, P. Terrier, C. Le Pechoux, J. Domont, J. Bénard, A. Le Cesne
Journal: Journal of Clinical Oncology (2007)

10074 Background: The impact of histological response (± 95% of necrosis) on patients (pts) outcome with LASTS treated by induction chemotherapy (CT) is still debated. Methods: From 1995 to 2005, 79 LASTS pts received induction CT consisting in two cycles of API-AI regimen and results were already reported (Gomez-Abuin, ASCO 2004). ERCC1, HER2 and Topoisomerase IIa (TopoII) was assessed by IHC on initial biopsies after paraffin embedding and correlated to histological response and pts outcome. Results: The median age of the 43 males and 36 females was 43 years (yr) (range 18–68) and the median tumor size at diagnosis was 109 mm (range 10–250 mm). CR was achieved in 4 pts, PR in 25 pts, SD in 45 pts and PD in 5 pts. R0 surgery was possible in 82% of pts; histological necrosis (HN) after chemotherapy was &gt;95% in 25 pts, between 50–95% in 28 pts and &lt;50% in 25 pts (median HN was 70%). All pts but one received postoperative radiotherapy. Relapse occurred in 37 pts; local in 3, distant in 33 and both in 1. After a median follow-up of 48 months (9–118 months) 51 pts are alive. The 5 yr DFS and OS were 45% and 60% respectively. Multivariate analysis correlated median HN to a better EFS and a non grade 3 to a better OS. Regarding protein expression (54 pts analyzed), a higher protein expression of TopoII was correlated to a better EFS (p=0.032) by univariate analysis and to OS by multivariate analysis (p=0.025). ERCC1 protein expression was not related to EFS and/or OS. There is no correlation between over expression of both proteins and any percentage of HN. Conclusions: A high rate of HN (&gt; 70%) after induction chemotherapy treatment is predictive for a better EFS. TopoII expression seems to be a relevant early predictive marker for outcome of pts with LASTS treated with doxorubicine-containing induction CT. No significant financial relationships to disclose.
Comprehensive Evaluation of Rhythm Monitoring Strategies in Screening for Atrial Fibrillation
Authors: Søren Zöga Diederichsen, Ketil Jørgen Haugan, Christian Kronborg, Claus Graff, Søren Højberg, Lars Køber, Derk Krieger, Anders Gaarsdal Holst, Jonas Bille Nielsen, Axel Brandes, Jesper Hastrup Svendsen
Journal: Circulation (2020)

Background: Stroke is an increasing health problem worldwide. Atrial fibrillation (AF) is a major risk factor for stroke, and the attention given to AF screening is rising, as new monitoring technologies emerge. We aimed to evaluate the performance of a large panel of screening strategies and to assess population characteristics associated with diagnostic yield. Methods: Individuals with stroke risk factors but without AF were recruited from the general population to undergo screening with an implantable loop recorder. New-onset AF lasting ≥6 minutes was adjudicated by senior cardiologists. After continuous monitoring for &gt;3 years, complete day-to-day heart rhythm data sets were reconstructed for every participant, including exact time of onset and termination of all AF episodes. Random sampling was applied to assess the sensitivity and negative predictive value of screening with various simulated screening strategies compared with the implantable loop recorder. The diagnostic yield across strategies and population subgroups was compared by use of nonparametric tests. Results: The rhythm data sets comprised 590 participants enduring a total of 659 758 days of continuous monitoring and 20 110 AF episodes. In these data, a single 10-second ECG yielded a sensitivity (and negative predictive value) of 1.5% (66%) for AF detection, increasing to 8.3% (67%) for twice-daily 30-second ECGs during 14 days and to 11% (68%), 13% (68%), 15% (69%), 21% (70%), and 34% (74%) for a single 24-hour, 48-hour, 72-hour, 7-day, or 30-day continuous monitoring, respectively. AF detection further improved when subsequent screenings were performed or when the same monitoring duration was spread over several periods compared with a single period (eg, three 24-hour monitorings versus one 72-hour monitoring; P &lt;0.0001 for all comparisons). The sensitivity was consistently higher among participants with age ≥75 years, male sex, CHADS 2 score &gt;2, or NT-proBNP (N-terminal pro-B-type natriuretic peptide) ≥40 pmol/L and among participants with underlying ≥24-hour AF episodes compared with shorter AF ( P &lt;0.0001 for all screening strategies). Conclusions: In screening for AF among participants with stroke risk factors, the diagnostic yield increased with duration, dispersion, and number of screenings, although all strategies had low yield compared with the implantable loop recorder. The sensitivity was higher among participants who were older, were male, or had higher NT-proBNP. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02036450 .
Drug use: more enforcement is unlikely to be the answer to rising harms, review finds
Authors: Richard Hurley
Journal: BMJ (2020)

Deaths from drugs in the UK are at an all time high, the market is increasingly violent, and drugs cost society £19bn (€22.3bn; $24.5bn) a year—more than double the worth of the market—an independent review has found.1

Some drugs are more available than takeaway pizza, said Carol Black, former president of the Royal College of Physicians, who conducted the review. She was speaking at a drug summit convened by the UK government in Glasgow on 27 February.

The UK faces a “perfect storm” of increasing supply, availability, and purity of drugs such as heroin, cocaine, and cannabis, coupled with reduced protections for vulnerable people, including 20% cuts …
Safety and efficacy of self‐administered romiplostim in patients with immune thrombocytopenia: Results of an integrated database of five clinical trials
Authors: David J. Kuter, Donald M. Arnold, Francesco Rodeghiero, Ann Janssens, Dominik Selleslag, Robert Bird, Adrian Newland, Jiri Mayer, Kejia Wang, Robert Olie
Journal: American Journal of Hematology (2020)

Romiplostim self-administration by patients or caregivers may offer time/cost savings to healthcare professionals (HCPs) and convenience for patients who avoid weekly clinic visits. We performed an integrated analysis of five clinical trials to evaluate the efficacy and safety of romiplostim self-administration. Data were analyzed from adults with immune thrombocytopenia (ITP) who received weekly romiplostim via self-administration or from an HCP. Patients who achieved a stable romiplostim dose for ≥3 weeks (HCP group ≥5 weeks to provide an appropriate index date to enable comparisons with the self-administration group) with platelet counts ≥50 × 109 /L were eligible. In the self-administration (n = 621) vs HCP (n = 133) groups, respectively, median age was 53 vs 58 years, median time since primary ITP diagnosis was 3.7 vs 2.5 years, and median baseline platelet count at ITP diagnosis was 19.0 vs 20.0 × 109 /L. In the self-administration and HCP-dosed groups, median romiplostim treatment duration was 89 vs 52 weeks and median total number of doses was 81 vs 50, respectively. In the self-administration and HCP groups, respectively: 95.0% and 100.0% of patients achieved ≥1 platelet response (defined as weekly platelet count ≥50 × 109 /L without rescue medication in previous 4 weeks); the median percentage of weeks with a response was 94.5% and 95.9%; and rescue medication was used in 36.7% and 39.8% of patients. Self-administration did not adversely affect safety; duration-adjusted rates for all treatment-emergent adverse events (TEAEs) and bleeding TEAEs were numerically lower with self-administration. Romiplostim self-administration appears effective and well tolerated in eligible patients with ITP.
Abstract P1-18-27: Developing a novel combination therapy using EZH2i for HER2+ breast cancer
Authors: Marina Watanabe, Rysn Kuzmickas, Karen Cichowski
Journal: Cancer Research (2020)

Abstract The receptor tyrosine kinase (RTK) human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers and acts as a driver of tumor growth. Though there are FDA-approved agents in the clinic that specifically target HER2, metastatic HER2+ breast cancer remains incurable with a median overall survival of 56.5 months. In addition, the response rates of patients with metastatic disease vary considerably, with 20-50% and 60-80% of patients unresponsive to first- and second-line therapies respectively. Therefore, it is necessary to discover a new therapy able to overcome the therapeutic resistance of HER2+ breast cancer that currently leads to patient relapse, and ultimately, death. One approach that our lab has successfully used to develop more effective therapies for other tumor types is to co-target different oncogenic pathways for a more potent effect. A target of interest is the histone methyltransferase enhancer of zeste homolog 2 (EZH2), which is overexpressed in many cancer types including breast, prostate, bladder, gastric, lung, and hepatocellular carcinoma. Interestingly, in breast cancer, EZH2 is overexpressed in the more aggressive subtypes including HER2+. EZH2 expression levels correlate with a worse prognosis and parallels cancer progression. We chose to investigate the therapeutic potential of combining EZH2 inhibitors (EZH2i) with lapatinib, an FDA-approved HER2-targeted therapy for late stage HER2+ breast cancer. In vitro assays show that the combination has a potent cytotoxic effect and renders lapatinib-sensitive HER2+ breast lines more sensitive, and causes lapatinib-resistant lines to become sensitive. In addition, in vivo testing of both lapatinib-sensitive and resistant HER2+ xenografts showed potent regression with the combination, confirming the extremely promising results. Using RNA-Seq and ChIP-Seq, we have identified that the Rb/E2F pathway may be involved in the combination’s mechanism of action. We will identify the biological settings in which this combination may be most effective and elucidate its molecular mechanism of action. This work will not only validate a promising new therapeutic combination, but will also provide insight into additional vulnerabilities of HER2+ breast cancer, possibly leading to additional therapeutic strategies. Citation Format: Marina Watanabe, Rysn Kuzmickas, Karen Cichowski. Developing a novel combination therapy using EZH2i for HER2+ breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-27.
Nothing Informal About Family Caregiving—Reply
Authors: Madeline R. Sterling, Amy L. Shaw
Journal: JAMA Internal Medicine (2020)

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