tbuckley/cabot-search huggingface dataset:
PD-1 protein and gene expression in early breast cancer: Prognostic implications.
Authors: Ioannis Zerdes, Alexios Matikas, John Lövrot, Emmanouil G. Sifakis, François Richard, Christos Sotiriou, George Z. Rassidakis, Jonas C. S. Bergh, Antonios Valachis, Theodoros Foukakis
Journal: Journal of Clinical Oncology (2020)

545 Background: We have previously shown the prognostic value of PD-L1 protein and gene expression in early breast cancer (BC), however, the prognostic role of PD-1 expression remains unclear. Methods: The prognostic value of PD-1 in early BC was investigated using three different approaches: i) evaluation of PD-1 at the protein (IHC, immunohistochemistry in tissue microarrays) and mRNA levels in a retrospective patient cohort of 586 patients treated for early BC in Stockholm, Sweden between 1997-2005, ii) systematic review and trial-level meta-analysis of studies published in Medline, Embase, Cochrane Library and Web of Science Core Collection libraries on the prognostic value of PD-1 IHC expression, and iii) pooled analysis of transcriptomic data from 39 publicly available datasets for the prognostic capacity of PD-1 gene expression. Univariate and multivariable Cox regression models were used. Results: In the retrospective study cohort, PD-1 protein was significantly associated with biologically high-risk characteristics. PD-1 protein, but not gene expression, was correlated with improved overall survival (OS) (adjusted HR = 0.73, 95% CI 0.55 – 0.96, p = 0.023 and adjusted HR = 0.88, 95% CI 0.68 – 1.13, p = 0.307, respectively). In the trial-level meta-analysis, 4736 entries were initially identified and 15 studies, including our original cohort, fulfilled the predefined eligibility criteria. PD-1 IHC expression was not prognostic in unselected patients. However, a significant correlation to improved disease-free survival was seen within the triple-negative subtype (pooled multivariate HR = 0.57, 95% CI 0.29 – 0.90, p = 0.02). In the pooled gene expression analysis, PD-1 gene expression was associated with improved OS in the entire population (adjusted HR = 0.89, 95% CI 0.80 – 0.99, p = 0.025) and in basal-like (adjusted HR = 0.77, 95% CI 0.63 – 0.95, p = 0.014) tumors. Conclusions: PD-1 expression at the RNA and protein levels represent promising prognostic factors, especially in the triple-negative and basal-like subtypes. Standardization and further validation are needed prior to clinical implementation.
Phase I study of teclistamab, a humanized B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma (R/R MM).
Authors: Saad Zafar Usmani, Maria-Victoria Mateos, Hareth Nahi, Amrita Y. Krishnan, Niels W.C.J. van de Donk, Jesus San Miguel, Albert Oriol, Laura Rosiñol, Ajai Chari, Homer Adams, Suzette Girgis, Shun Xin Wang Lin, Tara Stephenson, Kristy Kemmerer, Jennifer Smit, Yusri A. Elsayed, Jeffrey R. Infante, Jenna D. Goldberg, Arnob Banerjee, Alfred L. Garfall
Journal: Journal of Clinical Oncology (2020)

100 Background: Teclistamab (JNJ-64007957) is a bispecific BCMA x CD3 antibody that induces T cell-mediated cytotoxicity against BCMA-expressing myeloma cells. Initial results from an ongoing study of teclistamab in RRMM (NCT03145181) are presented. Methods: Pts have MM and are RR to standard therapies. Primary objective for part 1 is to identify a recommended phase 2 dose(s). Multiple intravenous (iv) doses ± priming doses were explored. Adverse events (AEs) were graded per CTCAE v4.03 and cytokine release syndrome (CRS) per Lee et al 2014. Response was investigator-assessed using IMWG criteria; minimal residual disease (MRD) in bone marrow was assessed by next generation sequencing. Results: As of 31 Jan 2020, 66 pts had received iv teclistamab (0.3–270 µg/kg). Median age was 64 y (24–82), median prior therapies was 6 (2–14), 97% triple-class exposed, 83% triple-class refractory, and 38% penta-drug refractory. Most common treatment-related AEs (all grade) were CRS (56%), neutropenia (26%), and anemia (23%). CRS events were all grade 1–2 and generally confined to initial doses. 8% of pts had treatment-related neurotoxicity (3% grade ≥3), and 9% had infusion related reaction. Infection-related AEs were reported in 61% of pts (21% grade ≥3). 2 dose-limiting toxicities were reported: grade 4 delirium (resolved after 16 days) and grade 4 thrombocytopenia (resolved after 1 day). 36% of pts had treatment-related grade ≥3 AEs; neutropenia (20%) and anemia (14%) were most frequent. Only 1 grade 5 AE was reported (respiratory failure in the setting of pneumonia deemed unrelated by the investigator). PK results indicate that the half-life of teclistamab supports weekly dosing. On-target pharmacodynamic activity (T cell redistribution and activation along with transient release of cytokines) was observed at doses ≥9.6 µg/kg. Cytokine production was modulated with step-up dosing while T cell activation was maintained. 65 pts were evaluable for response. Activity was observed starting at treatment doses ≥38.4 µg/kg, with 20/52 (38%) pts achieving a response. At the highest dose, 7/9 (78%) pts responded (1 response pending confirmation). Of MRD-evaluable pts who had complete response, 2/2 were MRD negative at 10 −6 with treatment ongoing &gt; 12 mo. Conclusions: Teclistamab has manageable safety across all doses explored. A 78% overall response rate was observed at the highest weekly treatment dose in pts with advanced RRMM, supporting further evaluation of teclistamab in expansion cohorts. Clinical trial information: NCT03145181.
Recent progress in acupuncture therapy for urine retention after anorectal surgical operations
Authors: 李伏蓉, 周爱生, 孙琰
Journal: BMJ (2005)

尿潴留是肛肠病手术后常见并发症,属中医癃闭范畴,系膀胱气化不利所致,以小便不利、涓滴而下,甚或小便不通为主证.对尿潴留的处理内服药多缓不解急,传统导尿法易诱发泌尿系逆行感染,患者不易接受,临床常采用针灸治疗本病,疗效满意.现就1996 年以来针灸治疗肛肠病术后尿潴留情况综述如下。
Early carcinoembryonic antigen (CEA) dynamics to predict fruquintinib efficacy in FRESCO, a 3+ line metastatic colorectal carcinoma (mCRC) phase III trial.
Authors: Yuxian Bai, Shukui Qin, Jin Li, Yanhong Deng, Lei Yang, Rui-hua Xu, Zhendong Chen, Haijun Zhong, Hongming Pan, Weijian Guo, Yongqian Shu, Ying Yuan, Jianming Xu, Lin Shen, Ning Wang, Bin Zhang, Qiang Zhang, Songhua Fan, Xiaojun Guo, Mengye Peng
Journal: Journal of Clinical Oncology (2020)

e16001 Background: The FRESCO phase 3 trial demonstrated a significant survival benefit with fruquintinib vs. placebo in the third-line or later therapy of mCRC patients. CEA levels are widely used in conjunction with imaging to monitor response to systemic therapy in patients with mCRC. Herein, we undertook post-hoc analyses of FRESCO patient data to investigate the early changes in CEA during treatment, as well as potential relationships with efficacy parameters. Methods: Patients were included if baseline CEA was abnormal according to local lab reference range. Serum CEA levels were measured at baseline and Day 1 of each cycle (except for Cycle 1). Early CEA change was analyzed at first radiological evaluation (C3D1, Week 8), CEA response was defined as ≥ 50% decrease from baseline, and CEA progression was defined as ≥ 100% increase from baseline. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated through Cox proportional hazards model; p-value was generated from log rank test. Results: 88.4% (245/277) and 94.9% (130/137) of patients had an abnormal baseline CEA in the fruquintinib group and placebo group, respectively. Median baseline CEA values were similar between treatment groups. After 2 cycles of treatment, the proportion of patients had CEA response was significantly higher in the fruquintinib group than placebo group (30.0% vs. 1.3%, p &lt; 0.001). In the fruquintinib group, patients with early CEA response (n = 63) had longer median OS (12.8 vs. 7.8 months, HR = 0.45, p &lt; 0.001) and median PFS (5.6 vs. 3.7 months, HR = 0.49, p &lt; 0.001) than patients without (n = 147). 66.7% (140/210) of patients in fruquintinib group had stable disease (SD), and fruquintinib in those patients with concomitant CEA response exhibited a significantly greater OS benefit than with CEA progression (14.4 vs. 8.7 months, HR = 0.38, p = 0.004). Conclusions: Fruquintinib increased early CEA response. CEA response at first radiological evaluation after cycle 2 could be considered as a predictor for better OS and PFS. Among patients with SD at first evaluation, those with CEA response seems benefit more from fruquintinib. Clinical trial information: NCT02314819 .
The impact of telemedicine on patient-reported outcomes in urologic oncology.
Authors: Adam John Gadzinski, Isabelle O. Abarro, Blair Stewart, John L. Gore
Journal: Journal of Clinical Oncology (2020)

e14154 Background: Nearly 20% of Americans live in rural communities. These individuals face barriers to accessing cancer care, including prevalent poverty and substantial travel burden to seeing cancer providers. We aimed to assess the impact of a rurally focused telemedicine program on patient outcomes in our urologic oncology outpatient clinic. Methods: We prospectively identified patients from rural Washington State, or who lived outside Washington, with a known or suspected urological malignancy being evaluated at the University of Washington Urology Clinic via an in person clinic or a telemedicine appointment. Patients were invited to complete a post-visit survey that assessed satisfaction, travel time, costs, and work absenteeism. We compared patient-reported outcomes between those seen as in-person versus telemedicine visits. Results: We invited 291 eligible patients from June 2019 – February 2020 to participate, 140 patients (48%) completed the survey. One-hundred and thirty-three patients had in person visits and 7 had telemedicine visits. Median age was 68, male 86%, and 69% Caucasian. Eighty-seven patients (62%) were from rural Washington; the remainder resided out-of-state. Patients were being evaluated for prostate cancer (57%), kidney cancer (18%), urothelial cancer (24%), and testis cancer (1%). Patient-reported outcomes are displayed in Table. Seventeen patients coming for in-person visits (13%) paid ≥ $1000 in total travel costs. No differences were noted in patient satisfaction. Conclusions: Patients traveling to our clinic from out-of-state and rural Washington incur significant travel time, costs, and time away from work to receive outpatient urologic cancer care. Telemedicine provides a medium for cancer care delivery that eliminates the significant travel burden associated with in person clinic appointments. [Table: see text]
Lipid levels and survival after obesity-related cancer in the Women’s Health Initiative CVD biomarker cohort.
Authors: Gayane Hovsepyan, Amy Lehman, Cynthia A. Thomson, Neil M. Iyengar, Jennifer Lynn Beebe-Dimmer, Ana Barac, Aladdin H. Shadyab, Theodore Brasky, Nazmus Saquib, Robert Wild, Pinkal Desai, Bette Jane Caan, Michael S. Simon
Journal: Journal of Clinical Oncology (2020)

e13618 Background: Previous investigations have demonstrated an inconclusive relationship between lipid biomarkers and mortality after cancer. Methods: We used data from 2,279 postmenopausal women diagnosed with 13 obesity-related cancers, who were part of the Women’s Health Initiative (WHI) lipid biomarkers cohort, to evaluate the relationship between lipid levels measured at study entry prior to cancer diagnosis, and mortality after cancer. Baseline lipid measurements consisted of HDL-Cholesterol, LDL-Cholesterol, and non-HDL-Cholesterol with ranges of measurement listed in the table. Obesity-related cancers included: meningioma, thyroid, adenocarcinoma of esophagus, breast, multiple myeloma, liver, kidney, gallbladder, stomach, uterus, pancreas, ovaries, and colorectal. The age adjusted relationship between baseline lipids and all-cause mortality as well as mortality due to cancer were estimated using Cox proportional hazards models and Fine-Gray models, respectively. Results: The majority of women in the cohort had either desirable or acceptable lipid levels (86% HDL-C, 30% LDL-C and 61% non-HDL-C. Low vs. desirable HDL-C levels were associated with higher risk of all-cause mortality (hazard ratio (HR) 1.54, 95% confidence interval [CI] [1.48, 1.60], p &lt;.001) and higher cancer mortality (sub-distribution hazard ratio (SHR)1.9, 95% CI [1.51, 2.3], p &lt;.001). High non-HDL-C vs desirable, was associated with higher all-cause mortality (HR 1.13, 95% CI [1.06, 1.21], p = .001) however no significant impact on cancer mortality (SHR 1.06, 95% CI [0.87, 1.30], p = 0.563). LDL-C levels demonstrated a more complex relationship with mortality, nevertheless, very high LDL-C levels were associated with higher risk of all-cause mortality (HR 1.63, 95% CI,1.21-2.2, p = ,0.001) and cancer-specific mortality (HR 1.78, 95% CI 1.22-2.63, p = 0.003). Conclusions: Elevated LDL-C and lower HDL-C may be associated with a lower risk of all-cause and cancer specific mortality in women diagnosed with obesity related cancers in the WHI. Results of multivariable adjustment for important predictors of mortality including race/ethnicity, medication use and other socio-demographic and clinical factors will be presented. [Table: see text]
A cross-sectional study on associated diseases in patients with gout and their diagnoses and therapy
Authors: Li-min Ren, Rong Mu, Zhan-guo Li
Journal: BMJ (2009)

Objective To investigate prevalence of associated diseases in patients with gout as well as their diagnoses and treatment. Methods Two hundreds out-patients diagnosed with gout from April to October 2008 were investigated at Peking University People's Hospital, and information collected included their general characteristics, associated diseases, diagnoses and treatment, as well as blood lipid profiles, serum creatinine, uric acid, results of routine urine tests and glomerular filtration rate estimated by MDRD formula in the past three months. Results Among patients with gout, prevalence of associated hypertension, obesity, renal calculi, coronary heart disease, cerebral infarction and diabetes were 54.5% (109/200), 23.2% (42/181), 20.0% (40/200), 12.0% (24/200), 8.0% (16/200) and 7.0% (14/200), respectively, and 53.7% (101/188) of them associated with hypertriglyceridemia, 63.7% (114/179) with impaired renal function and 15.1% (27/179) with chronic kidney disease. In acute attack of gout, 124 (62.0%) of them were treated with non-steroidal anti-inflammatory drug (NASID), 72 (36.0%) with colchicines, 12 (6.0%) with corticosteroid and 30 (15.0%) with urate-lowering drugs, respectively, and during its intermittent period, 69. 8% (81/116) of them received urate-lowering therapy with indications generally accepted internationally, but serum level of uric acid could be maintained below 0.06 g/L in only 8.6% (10/116) of them. And 73.8% (48/65) of the patients with no therapy indications also were treated with urate-lowering drugs. Conclusions The most commonly associated diseases in gout patients are hypertension, hyperlipidemia and obesity, followed by renal calculi, chronic kidney disease and coronary heart disease, and so on. At present, oral NSAID is the first choice of drugs for its acute attack. Indications for urate-lowering therapy in this hospital usually are not consistent with those by generally international acceptance, with lower therapeutic effectiveness achieved.

Key words: 
Gout;  Data collection;  Associated diseases
Clinical analyses of 2 preoperative chemotherapies for Ib2-IIb cervical cancer
Authors: Kunling Song, Yao Yang
Journal: BMJ (2014)

A total of 104 patients with cervical squamous cell cancer (Figo I b2-II b) were recruited during March 2006 and October 2011. One group (A, n=50) received preoperative intravenous neoadjuvant chemotherapy while another group (B, n=54) had interventional arterial chemotherapy plus bilateral uterine artery embolization. Surgery was performed for those with a change of cancer size either as complete or partial remission at Week 2 post-chemotherapy according to the WHO evaluation criteria. Otherwise radiotherapy was implemented. The ratio of surgery after chemotherapy was 70% (n=35) in Group A versus 87% (n=47) in Group B (P 0.05). Preoperative chemotherapy is effective for cervical squamous cancer (tumor diameter >4 cm) with fewer side effects.


Key words: 
Uterine cervical neoplasms; Antineoplastic combined chemotherapy protocol
Modulation of YAP/ TAZ by statins to improve survival in epithelioid hemangioendothelioma (EHE).
Authors: Aparna Subramaniam, Jing Zheng, Sudha Yalamanchili, Anthony Paul Conley, Ravin Ratan, Neeta Somaiah, J Andrew Livingston, Maria Alejandra Zarzour, Dejka M. Araujo, Robert S. Benjamin, Shreyaskumar Patel, Vinod Ravi
Journal: Journal of Clinical Oncology (2020)

e23527 Background: EHE is a rare soft tissue tumor of endothelial origin. It is distinguished by the pathognomonic WWTR1-CAMTA1 fusion (WWTR1 is the gene symbol for TAZ) seen in 90% of the tumors. YAP1-TFE3 fusion is less common and seen in 10% of the tumors. YAP and TAZ are critical downstream effectors of the Hippo pathway that regulate tumor development, progression, invasion and metastasis by modulating the expression of many Hippo pathway targets. Recent studies have shown that inhibition of HMG-CoA reductase, a key enzyme of the mevalonate pathway, can regulate YAP/ TAZ by preventing their nuclear accumulation and inhibiting their transcriptional activity. This has led to interest in the role of statins, which inhibit HMG-CoA reductase, as a modulator of YAP/ TAZ that could benefit patients with sarcoma, particularly EHE. Methods: A retrospective analysis was performed on patients with a diagnosis of EHE at M D Anderson Cancer Center. Patients were identified using the electronic database system and screened for statin use using EMRs. Demographic and clinical characteristics were tabulated. KM method was used to assess overall survival and log rank test was used to test survival differences between the statin use and non- statin use groups. All statistical analysis was performed using STATA 14. Results: 226 patients with EHE were identified. 27 of them had recorded statin use during the course of their disease. The median OS for the statin use group was not reached and the mean OS was 221 months. The median OS for the non- statin use group was 123.9 months, while the mean OS was 160 months. The difference in OS was not statistically significant between the two groups. The median follow-up time for our cohort was 36.6 months. Conclusions: Our findings indicate a trend towards improved survival for patients with EHE who have received statins over the course of their disease. Our study is limited by a small number of patients who received statins. Prospective studies are required to assess the therapeutic benefit of statins in EHE. [Table: see text]
Hydroxychloroquine-induced depressive disorder in patients with systemic lupus erythematosus: case report and literature review
Authors: Liping Wang, Chunyan Wang, Xuqiang Jia, Xiaojun Zhao, Rui Zhang
Journal: BMJ (2018)

Three patients with systemic lupus erythematosus(SLE) were admitted in Lanzhou University Second Hospitalbetween May 2013 and October 2017, the patients were treated with hydroxychloroquine(HCQ) for SLE.Patients had no neuropsychiatric symptoms before HCQ treatment, depressive symptoms occurred in 2 cases when the SLE was stable, and 1 case had renal function damage and depressive symptoms. The diagnosis of depression was confirmed in all 3 cases. The treatment for neuropsychiatric lupus was given but of no effect, while the symptoms disappeared after withdraw of HCQ. There is no difference in clinical manifestations between HCQ-caused depressive disorder and depression in neuropsychiatric lupus, but the treatment is different.The literature was searched from 1992 to 2018, and 4 cases of neuropsychiatric disorders caused by HCQ were reported, of which 3 were diagnosed as SLE, and 1 case was chronic Q fever. When depression appears in SLE patients receiving HCQ, HCQ would be the cause and the medication of HCQ should be withdrawn if necessary.


Key words: 
Hydroxychloroquine; Lupus erythematosus, systemic; Depressive disorder
Front-line daratumumab in newly diagnosed AL amyloidosis patients.
Authors: Vanessa Elaine Kennedy, Nina Shah, Jeffrey Lee Wolf, Thomas G. Martin, Sandy Wai Kuan Wong
Journal: Journal of Clinical Oncology (2020)

e20569 Background: Light chain amyloidosis (AL) is a plasma cell dyscrasia characterized by organ dysfunction, morbidity, and early mortality. Treatment focuses on suppressing monoclonal light chain production as measured by hematologic response criteria (Comenzo et al., 2012). Daratumumab (DARA), a monoclonal CD38 antibody, has demonstrated efficacy in heavily pretreated AL patients (Kaufman et al., 2017). We report the outcomes of newly diagnosed AL patients treated with a DARA-based regimen. Methods: A single-center retrospective chart review with an IRB-approved protocol was performed on newly diagnosed AL patients treated with first line DARA-based regimens between 1/2018 – 12/2019. Results: Fourteen patients were evaluated. The median age was 69 years (45 – 87), 50% were male, and 50% produced monoclonal lambda light chains. All patients had cardiac and renal involvement. Per the 2004 Mayo staging system, 1/14 (7%) patients had stage I cardiac disease, 2/14 (14%) had stage II, and 11/14 (79%) had stage III, of which two were stage IIIb. Regarding renal staging (Palladini et al., 2014), 10/14 (71%) patients were stage I, 3/14 (21%) stage II, and 1/4 (7%) stage III. Most patients (11/14) received DARA in combination with bortezomib and dexamethasone, while one patient received DARA and dexamethasone (DEX). Two patients received DARA in combination with bortezomib, cyclophosphamide, and DEX. Patients received a median of 5 cycles of DARA (1 – 14). After a median follow-up of 4.4 months (1 – 19), all patients were still receiving DARA. DARA was well tolerated, with 4 patients (29%) experiencing grade 1 infusion reactions and no additional toxicities observed. Responses were rapid, with a median time of 11 days (7 – 61) to first response and 46 days (9 8– 168) to best response. First response was classified as partial response (PR) in 8/14 patients (57%), very good PR (VGPR) in 3/14 (21%), and complete response (CR) in 1/14 (7%). Best response included a PR in 3/14 (21%), VGPR in 7/14 (50%), and CR in 2/14 (14%). In most patients, responses deepened over time. Cardiac response was seen in 5/7 (71%) evaluable patients with median time to response of 39 days (21 – 263). Renal response was seen in 2/4 (50%) evaluable patients with median time to response of 152 days (94 – 194). Conclusions: First line use of DARA in AL amyloidosis produced rapid and deep hematologic and organ response, resulting in a 93% objective hematologic response rate. DARA was well-tolerated and efficacious even among patients with extensive organ involvement and cardiac dysfunction. Prospective studies of first line DARA are warranted.