tbuckley/cabot-search huggingface dataset:
A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC).
Authors: Adrienne Gropper Waks, Tanya Keenan, Tianyu Li, Nabihah Tayob, Gerburg M. Wulf, Edward T. Richardson, Elizabeth A. Mittendorf, Beth Overmoyer, Ian E. Krop, Eric P. Winer, Eliezer Mendel Van Allen, Judith Agudo, Sara M. Tolaney
Journal: Journal of Clinical Oncology (2020)

1046 Background: Preclinical evidence suggests treatment (tx) with T-DM1 plus an anti-PD1 antibody triggers antitumor immunity. We conducted a phase 1 trial to determine the safety and explore the efficacy of T-DM1 plus pembro. Methods: Eligible patients (pts) had MBC previously treated with trastuzumab (H) and taxane (T), were T-DM1-naïve, and received &gt;1 prior line of tx for MBC or developed recurrence within 6 months (mo) of adjuvant tx. A dose de-escalation (esc) design was used with 6 pts in the dose-finding cohort, followed by an expansion (exp) cohort at the recommended phase 2 dose (RP2D), with mandatory baseline biopsies (bx). The primary endpoint was safety and tolerability. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and clinical benefit rate (CBR: complete response + partial response + stable disease &gt;24 weeks). Associations between immune biomarkers and tx response were explored. Results: 20 pts started protocol tx (6 in dose de-esc cohort; 14 in exp cohort). Median follow-up was 23.5 mo. Pts had median age 54 yrs and median 1 line of prior MBC tx (range 0-2); 100% had received prior T, H, and pertuzumab. There were no dose-limiting toxicities in the dose de-esc cohort; thus full doses of T-DM1 (3.6 mg/kg q21 days) and pembro (200 mg q21 days) were the RP2D. 85% of pts experienced tx-related adverse events (AEs) &gt; grade (gr) 1; 20% of pts experienced gr3 AEs. There were no gr&gt;4 AEs. Gr3 AEs were fatigue; AST increase; ALT increase; pneumonia; pneumonitis; oral mucositis; and vomiting, each in 1 pt. 17 pts had baseline bx; 6 pts had repeat bx after 1 tx cycle. Efficacy results, overall and by PD-L1 Combined Positive Score (CPS; 22C3 staining) and tumor-infiltrating lymphocyte (TIL) status, are shown in the table. Tumors’ antigen presentation will be explored through HLA/dendritic cell marker staining and immune signatures by RNA sequencing. Conclusions: T-DM1 plus pembro was safe and tolerable. The regimen demonstrated clinical activity. Further exploration of immune-related predictive biomarkers is warranted. Clinical trial information: NCT03032107 . [Table: see text]
Association of immune related adverse events with superior outcomes in patients with hepatocellular carcinoma (HCC) treated with nivolumab.
Authors: Lorena Ostios-Garcia, David Ramiro-Cortijo, Mary Linton Bounetheau Peters, Andrea J. Bullock
Journal: Journal of Clinical Oncology (2020)

e16630 Background: Nivolumab, an anti-PD1 antibody, is FDA approved in patients (pts) with HCC. Anti-PD-1 promotes hyperstimulation of host immunity and is associated with a spectrum of toxicities known as immune-related adverse events (irAEs). In other malignancies, higher rates of irAEs are associated with improved cancer outcomes. This study shows correlation between irAEs and efficacy in pts with HCC treated with nivolumab. Methods: Demographic and toxicity data were collected retrospectively on all pts with HCC treated with nivolumab at a single institution from Jan 2012 – Sept 2019. Response was evaluated using RECISTv1.1. Adverse events were assessed according to CTCAEv5.0. Categorical variables were assessed by Fisher's exact test. Survival was estimated with the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed by the Cox-regression model. Results: 30 pts were treated; irAEs were detected in 16 (53%). There was no difference in baseline characteristics among those who did and did not experience irAEs (Table). The most frequent irAEs were elevated AST/ALT (n = 7; 44%), rash (n = 4; 25%), and hypothyroid (n = 4; 25%). 3 G3 (rash and transaminitis) and 1 G4 AE (pured red cell apalasia) were observed. Among all pts, overall response rate (RR) and disease control rate (DCR) were 13 and 50%, respectively. Median progression free survival (PFS) and overall survival (OS) were 27 and 56 weeks (w), respectively. The RR and DCR were higher among irAEs vs non-irAEs, although this did not reach statistical significance (RR 25 vs 0%; p = 0.05; DCR 62 vs 35%; p = 0.19). Median PFS and OS were longer in those with irAEs vs non-irAE; PFS 33 vs 16 w (HR: 0.26; CI 95%: 0.076-0.89; p = 0.028); (OS 69 vs 21 w HR: 0.18; CI 95%: 0.05-0.58; p = 0.002). On multivariate analysis, viral etiology was associated with prolonged PFS (p = 0.002) and MELD was associated with reduced OS (p = 0.004). Conclusions: Development of irAEs was associated with prolonged PFS and OS in pts with HCC treated with nivolumab. Further study is needed to determine whether type of irAE, onset time, or duration affect cancer outcomes. [Table: see text]
Changes of plasma brain natriuretic peptide and its clinical significance in patients with atrial fibrillation
Authors: Ying Feng
Journal: BMJ (2008)

Objective To study the changes of plasma brain natriuretic peptide(BNP)level in patients with atrial fibrillation(AF),and explore the relationship between plasma level of BNP and paroxysmal AF,persistent AF,rheumatic AF and non-rheumatic AF.Methods In total,158 outpatients and inpatients diagnosed as heart diseases were selected from the Affiliated Hospital of Inner Mongolia Medical College during October 2005 to January 2007,83 with AF and 75 without AF.Their cardiac function Was evaluated according to the classification system of the New York Heart Association(NYHA)in the United States.Plasma level of BNP was measured with bi-monoclonal antibody microparticulate enzyme immunoassay(MEIA).Results Plasma BNP level was significantly higher in AF group[(112±75)ng/L]than that in non-AF group[(39±26)ng/L,P＜0.05]with same ventricular function.No significant difference in plasma level of BNP between the groups with paroxysmal AF[(113±84)ng/L]and with persistent AF[(110±69)ng/L]was found.Plasma level of BNP Was(84±73)ng/L in the group with rheumatic valvular AF,not significantly different from that in non-valvular AF[(117±76)ng/L,P＞0.05].Conclusion Plasma BNP level is higher in AF group than that in non-AF group,but no significant difference in plasma BNP level between patients with paroxysmal AF,persistent AF,rheumatic valvular AF and non-rheumatic AF,under same ventricular function,was found.

Key words: 
Natriuretic peptide,brain; Atrial fibrillation
Thoracic paravertebral block for patients undergoing video-assisted thoracoscopic surgery
Authors: Lixin Sun, Qiang Wang, Fuguo Ma, Nianguo Hou
Journal: BMJ (2016)

对行胸腔镜肺叶切除、淋巴结清扫治疗的50例患者，分别采用胸椎旁神经阻滞(P组，25例)、单纯全麻(G组，25例)，术后P组行胸椎旁神经自控镇痛，G组行静脉自控镇痛。比较术后疼痛视觉模拟评分(VAS)及镇静评分、术后周转时间、术后48 h呼吸功能以及血CRP、皮质醇、血管紧张素Ⅱ(ATⅡ)水平。P组术后12～48 h的VAS及镇静评分低于G组[P组(2.4±0.5)～(3.8±1.3)分，G组(3.1±0.8)～(4.6±1.5)分；P组(2.0±0.4)～(2.3±0.5)分，G组(2.4±0.4)～(2.7±0.5)分，均P<0.05]；P组拔管及监护室滞留时间明显短于G组[(6.2±1.8)与(7.5±2.2)min，(14.3±3.5)与(17.2±4.2)h，均P<0.05]；P组术后的用力肺活量(FVC)和第1秒用力肺活量明显高于G组[(69±16)与(60±13)%，(59±13)与(51±10)%，P<0.05]，PaCO2明显低于G组[(40.8±2.5)与(43.2±2.8) mmHg(1 mmHg＝0.133 kPa)，P<0.05]；P组患者术毕及术后24 h CRP、皮质醇及ATⅡ水平均低于G组(P<0.05)。提示胸椎旁神经阻滞用于胸腔镜手术患者可减轻术后疼痛、控制应激反应，并加快周转。
Long-Term Care Policy after Covid-19 — Solving the Nursing Home Crisis
Authors: Rachel M. Werner, Allison K. Hoffman, Norma B. Coe
Journal: New England Journal of Medicine (2020)

Long-Term Care Policy after Covid-19 Covid-19 has exposed the cracks in the U.S. system of providing and funding long-term care, and there are no easy fixes. We need comprehensive policies that tak...
Expanded Imaging Classification of Autosomal Dominant Polycystic Kidney Disease
Authors: Kyongtae T. Bae, Tiange Shi, Cheng Tao, Alan S. L. Yu, Vicente E. Torres, Ronald D. Perrone, Arlene B. Chapman, Godela Brosnahan, Theodore I. Steinman, William E. Braun, Avantika Srivastava, Maria V. Irazabal, Kaleab Z. Abebe, Peter C. Harris, Douglas P. Landsittel
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Accurate prediction of risk for disease progression is crucial for clinical management of autosomal dominant polycystic kidney disease (ADPKD). The Mayo imaging classification of ADPKD uses height-adjusted total kidney volume (htTKV) and age to identify patients at highest risk. Because the current Mayo classification applies only to patients with typical diffuse cystic disease (class 1) and poorly predicts eGFR decline for the remaining 5%–10% of patients with atypical morphology (class 2), imaging-based risk modeling remains unresolved. The authors report an expanded imaging classification model in which use of a recalculated htTKV value that excludes prominent exophytic cysts improved prediction for eGFR trajectory. Using a recalculated htTKV may allow inclusion of class 2 patients in the Mayo classification of ADPKD and reclassification of class 1 patients with prominent exophytic cysts. Background The Mayo Clinic imaging classification of autosomal dominant polycystic kidney disease (ADPKD) uses height-adjusted total kidney volume (htTKV) and age to identify patients at highest risk for disease progression. However, this classification applies only to patients with typical diffuse cystic disease (class 1). Because htTKV poorly predicts eGFR decline for the 5%–10% of patients with atypical morphology (class 2), imaging-based risk modeling remains unresolved. Methods Of 558 adults with ADPKD in the HALT-A study, we identified 25 patients of class 2A with prominent exophytic cysts (class 2Ae) and 43 patients of class 1 with prominent exophytic cysts; we recalculated their htTKVs to exclude exophytic cysts. Using original and recalculated htTKVs in association with imaging classification in logistic and mixed linear models, we compared predictions for developing CKD stage 3 and for eGFR trajectory. Results Using recalculated htTKVs increased specificity for developing CKD stage 3 in all participants from 82.6% to 84.2% after adjustment for baseline age, eGFR, BMI, sex, and race. The predicted proportion of class 2Ae patients developing CKD stage 3 using a cutoff of 0.5 for predicting case status was better calibrated to the observed value of 13.0% with recalculated htTKVs (45.5%) versus original htTKVs (63.6%). Using recalculated htTKVs reduced the mean paired difference between predicted and observed eGFR from 17.6 (using original htTKVs) to 4.0 ml/min per 1.73 m 2 for class 2Ae, and from −1.7 (using original htTKVs) to 0.1 ml/min per 1.73 m 2 for class 1. Conclusions Use of a recalculated htTKV measure that excludes prominent exophytic cysts facilitates inclusion of class 2 patients and reclassification of class 1 patients in the Mayo classification model.
Assessment of multidisciplinary disease care model for outpatients with first-episode and high-risk ischemic strokes
Authors: Yang Jin, Aiyan Shao, Ying Sun, Li Zhou, Haifang Dong, Su Qian, Xiangyang Cao, Mingchao Li, Lijun Wang
Journal: BMJ (2015)

A total of 218 outpatients with first-episode and high-risk ischemic strokes were randomly divided into management and control groups. Management group received multidisciplinary disease care mode while control group common disease care mode. The results showed that the functional independent measures (FIM) score of management group improved dramatically (89±28 vs. 81±26, P=0.04). The National Institutes of Health Stroke Scale (NIHSS) score changed significantly (13.9±5.6 vs. 16.1±6.9, P=0.02). Systolic blood pressure significantly changed [(131±17) vs. (137±23) mmHg(1 mmHg=0.133 kPa), P=0.04]. Diastolic blood pressure significantly changed [(81±10) vs. (85±15) mmHg, P=0.03]; Low density lipoprotein decreased [(2.54±0.75) vs. (2.81±0.65) mmol/L, P=0.01]. The number of readmitted patients also decreased significantly (P=0.04). Thus multidisciplinary disease care mode could enhance the quality-of-life, control risk factors and improve patient prognosis.


Key words: 
Stroke; Disease Monagement
Clinicopathological features and prognosis of rare carcinomas of the breast: A comparative analysis from the NCDB.
Authors: Elizabeth Blessing Elimimian, Thomas A. Samuel, Hong Liang, Nadeem Bilani, Leah Elson, Zeina A. Nahleh
Journal: Journal of Clinical Oncology (2020)

e19256 Background: A comparative analysis of the clinicopathological features, immunohistochemistry, and overall (OS) for rare ( &lt; 10%) of all breast cancers (BCs) has not been widely explored. Methods: The National Cancer Database (NCDB) was reviewed for patients with a confirmed diagnoses of the following rare BC tumors: Mucinous adenocarcinoma (MuC), tubular adenocarcinoma (TuC), intraductal micropapillary (IMP), papillary carcinoma (PaC), and intraductal papillary adenocarcinoma (IPA) between 2010 and 2016. Patients with an unknown stage were excluded. Univariate analyses &amp; multivariable Cox-regression models were performed in SAS v. 9.4. Results: Analysis included 70,341 patients. MuC was the most common histologic type seen among the rare tumors in our cohort n = 30,087 (43%), compared with 9,681 (13.8%) TuC, 12,735 (18.1%) IMP, 435 ( &lt; 1%) PaC, &amp; 17,403 (24.7%) IPA. TuC &amp; IMP both presented earlier in life, with a median age of 60 versus 69 years for MuC patients and 67 years for both PaC &amp; IPA. The majority of carcinomas were ER+/PR+/HER2- (MuC 88.6%, TuC 89.9%, IMP 67.3%, PaC 76.8%, &amp; IPA 79.6%); ER+/PR+/HER2+ were noted in 3.5% of Muc and 13.2 % of IMP, and ER-/PR-/HER2- were seen in PaC 8.7% and IPA 7.3%. Two highly significant factors for inferior outcome were stage (III &amp; IV) and metastasis to the brain. Stage ≥3 at diagnosis conferred a worse prognosis for MuC patients (HR 3.1, p &lt; 0.0001), IPA patients (HR 3.5, p &lt; 0.0001), &amp; IMP patients (HR 4.8; p &lt; .0001) when compared to patients with stage 0 &amp; 1. Brain metastasis was an adverse mortality indicator for MuC patients (HR 2.4, p &lt; .0003), IPA patients (HR 6.8, p &lt; 0.0001), &amp; IMP patients (HR 10.4, p &lt; .0001). For MuC, age ≥60 was also prognostic (HR 2.7; p &lt; .0001). The 5-year OS was 92.2% for patients with MuC, 94.7% for TuC patients, 93.1% for IMP patients, 81% for PaC &amp; 90% for IPA overall (p-values &lt; 0.0001). Conclusions: The rare BC tumors analyzed in this large database confirm that these tumors are typically seen at an older age, are commonly ER+/PR+/HER2 -, and rarely HER2 + or Triple negative. Mucinous adenocarcinoma being the most common type. They have an overall good prognosis, with papillary carcinoma having inferior OS. Other poor prognostic factors include older age, brain metastasis and advanced stages at diagnosis.
Mutational profile of hepatocellular carcinoma by liquid biopsy of Hispanics in central California.
Authors: Mir Ali, Uzair Bashir Chaudhary, Salimah Valliani, Shirley Kim, Diana Moers, Hugo Akabane, Amir Fathi
Journal: Journal of Clinical Oncology (2020)

e16621 Background: Hepatocellular carcinoma (HCC) when localized to liver is typically diagnosed with Characteristic radiographic features while tumor tissue sampling is not warranted anymore. Recently, circulating tumor DNA (ctDNA) has been used to evaluate mutational profile in solid tumors in order to personalize treatments. However, it is not established well in HCC, specifically in Hispanic patients. This study aims to describe the mutational profile of Hispanic patients with ctDNA analysis as a single center experience. Methods: We enrolled 33 patients with diagnosis of HCC from 1/2016 to 12/2019. Diagnosis of HCC was based on Characteristic radiological features, defined by Liver Imaging Reporting and Data System (LI-RADS category 5). 18 patients self-identified as Hispanic while remaining were mainly Caucasians. FoundationOne Liquid genomic testing by Foundation Medicine was used for profiling of 77 most commonly mutated genes of sampled blood. Results: Baseline patient characteristics were similar between Hispanic and non-Hispanic population. Median age of diagnosis was 64 in this cohort with 23(70%) males and 10(30%) females. 30 patients had underlying cirrhosis with hepatitis C present in 19(58%) and heavy alcohol abuse in 15(45%) of cirrhotic. 32 patients had liver-only disease, while we had one patient with extrahepatic disease. 22 of these 33 patients had a single HCC lesion while 11 had multifocal HCC. 20 patients (60.6%) had at least 1 pathogenic mutation. 13 patients (39.4%) did not have any pathogenic mutations. The frequency of commonly mutated genes for our Hispanics versus non-Hispanics were following: CTNNB1(45.5% vs 44.4%), TERT (45.5% vs 55.6%), TP53(36.4% vs 55%), CNK2A (18.2% vs 0). Median of Allele frequency percentage was 0.81%. Mutations in TP53 was commonly detected at codon 249(R249S). Presence of these pathogenic mutations were associated with poor clinical features such as multifocal disease and higher AFP values &gt; 59 as compared to 15 without mutations. Other mutations present at lower percentage include ERBB2, PIK3CA, DNMT3A, GNAS, KDR, RB1, PTEN and their frequency was similar in both Hispanic and non-Hispanic groups. Conclusions: Genomic profiling of ctDNA by liquid biopsy in our Hispanic patients with HCC appears similar to established mutational profile of HCC in Caucasian and Asian populations. These findings can be verified in heterogeneous populations in order to serve as a potential prognostic tool and help with personalized medicine.
Gender-based disparities in clinical trials supporting FDA approval of oncology drugs.
Authors: Marjorie Zettler, Bruce A. Feinberg, Jonathan Kish, Ajeet Gajra
Journal: Journal of Clinical Oncology (2020)

2058 Background: Adequate gender representation in clinical trials of new drugs is critical in order to accurately detect possible differences in response and toxicity (Özdemir et al, JCO 2018). The under-representation of women in oncology clinical trials has been previously described, however data on registrational trials, which are the basis for drug approval and inform the prescribing information, is lacking. We conducted an analysis of the trials supporting Food and Drug Administration approval of oncology drugs over a 5-year period to evaluate the representation of women vs. men. Methods: Prescribing information for novel new drugs approved from 2014-2018 was reviewed for the proportions of men and women in the evaluable population of the supporting clinical trials. Sex-specific cancers were excluded. Prevalence estimates for the indications were obtained from the Surveillance, Epidemiology and End Results database and the published literature. A participation to prevalence ratio (PPR) was calculated for each trial by dividing the percentage of women in the trial by the percentage of women in the disease population. A PPR value closer to unity represents even gender distribution and the range 0.8-1.2 is considered to reflect an acceptable representation of women. Data are presented using descriptive statistics. Results: A total of 46 oncology drugs were approved based on 56 trials enrolling 13,862 patients (7941 [57%] men; 5,921 [43%] women). Of the 56 trials, 38 (68%) had a PPR within the 0.8-1.2 range, 15 (27%) fell between 0.4-0.7, and 3 (5%) had a PPR of 1.3. The proportion of trials with unbalanced gender representation was comparable for hematological malignancy and solid tumor indications and did not improve over time. Fewer unbalanced trials were Phase III or employed a randomized design. Nine of the 18 (50%) unbalanced trials enrolled &lt;100 subjects, compared to 3 of the 38 (8%) balanced trials. Conclusions: A third of registrational trials for oncology drugs lacked balanced gender distribution. Of the trials lacking balance, the vast majority (80%) had under-representation of women. Phase I-II trials and smaller trials had greater gender disparity, a concerning finding in a precision medicine environment where an increasing number of registration trials have double digit accrual. Further research is needed to understand the implications of unbalanced gender accrual in registrational trials, and to develop strategies for preventing disparities.
Updated overall survival (OS) and safety data from the randomized, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced <i>ALK</i>+ NSCLC.
Authors: Solange Peters, Tony S. K. Mok, Shirish M. Gadgeel, Rafael Rosell, Rafal Dziadziuszko, Dong-Wan Kim, Maurice Perol, Sai-Hong Ignatius Ou, Alice Tsang Shaw, Walter Bordogna, Vlatka Smoljanovic, Magalie Hilton, Thorsten Ruf, Venice Rosale Archer, D. Ross Camidge
Journal: Journal of Clinical Oncology (2020)

9518 Background: Final, mature PFS from the global phase III ALEX study (NCT02075840) of ALC vs CRZ in untreated, advanced/metastatic ALK+ NSCLC have been previously published: ALC 34.8 months (m) (95% CI 17.7–NR) vs CRZ 10.9 m (95% CI 9.1–12.9), (HR 0.43, 95% CI 0.32–0.58). We report 5-year OS and updated safety data from ALEX with a further 12 m follow-up (FU) (cutoff date: Nov 29, 2019). Methods: Patients (pts) with stage IIIB/IV ALK+ NSCLC (by central IHC), ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC were randomized 1:1 to ALC 600 mg BID (n = 152) or CRZ 250 mg BID (n = 151). Asymptomatic CNS metastases (mets) at baseline (BL) were allowed. OS was a secondary endpoint, and no formal statistical testing was planned. Results: Median duration of FU: 48.2 m with ALC vs 23.3 m with CRZ. OS data remain immature (events: 37%; stratified HR 0.67 [95% CI 0.46–0.98]); median OS with CRZ was 57.4 m (95% CI 34.6–not estimable [NE]) vs NE with ALC. The 5-year survival rate was 62.5% (95% CI 54.3–70.8) with ALC vs 45.5% (95% CI 33.6–57.4) with CRZ (Table). In pts with CNS mets at BL the OS HR was 0.58 (95% CI 0.34–1.00) and 0.76 (95% CI 0.45–1.26) in pts without CNS mets at BL. The OS benefit of ALC vs CRZ was generally consistent across all subgroups. Considering the longer treatment duration for ALC (28.1 m) vs the previous analysis (27.7 m), the safety profile of ALC remains consistent; no new safety signals were observed. With ALC, 35% of pts remain on study treatment vs 9% of pts remaining on CRZ. In pts with ≥1 known post-progression treatment (ALC: 32.2%; CRZ: 45.7%), lorlatinib was the most common ALK TKI received after first-line ALC (7.2%), compared with ceritinib after first-line CRZ (15.2%). Conclusions: This is the first global randomized study of a 2 nd generation ALK TKI to demonstrate a clinically meaningful improvement in OS vs CRZ in ALK+ NSCLC (5-year survival rate: 62.5%, ALC vs 45.5%, CRZ); longer FU is required as OS data remain immature. Clinical trial information: NCT02075840 . [Table: see text]