tbuckley/cabot-search huggingface dataset:
Myometrial invasion in endometrial cancer: diagnostic performance of diffusion-weighted magnetic resonance imaging 3.0-T
Authors: Jun Sun, Wen-xin Chen, Jing Ye, Shou-an Wang, Bin-bin Shi, Jian-xiong Fu
Journal: BMJ (2013)

A total of 68 patients with histologically proven endometrial cancer were preoperatively evaluated with a 3.0 T magnetic resonance (MR) unit. Two radiologists interpreted the depth of myometrial invasion on T2-weighted and diffusion-weighted(DW)MR (b=700 s/mm2) imaging. Myometrial tumor spread was classified as superficial (<50%) or deep (≥50% myometrial thickness). Statistical methods included Kappa statistics for reader agreement, accuracy assessment and receiver operating characteristic analysis for diagnostic performance comparison. For assessing the depth of myometrial invasion, the diagnostic accuracy, sensitivity and specificity were as follows: T2-weighted imaging-reader 1st, 61.8%, 60.0% and 65.2%; reader 2nd, 66.2%, 64.4% and 69.6%; T2-weighted combined DW imaging-reader 1st, 86.8%, 84.4% and 91.3%; reader 2nd, 89.7%, 86.7% and 95.7%. Reader agreement was excellent for T2-weighted combined DW imaging (Kappa=0.818). For assessing deep myometrial involvement, ROC analysis showed that the diagnostic accuracy was significantly higher on T2-weighted combined DW imaging than that on T2-weighted imaging. The AUC (area under the curve) values measured by two readers on T2-weighted and T2-weighted combined DW imagings were 0.626, 0.879 and 0.670, 0.912 respectively. The addition of 3.0T MR diffusion-weighted to T2-weighted imaging can improve the diagnostic performance of MR imaging in the assessment of myometrial invasion.


Key words: 
Endometrial neoplasms; Diffusion-weighted imaging
Patient knowledge and expectations of anti-cancer treatments in the advanced disease setting.
Authors: Darren Cowzer, Maeve Hennessy, Anna Linehan, zac coyne, Daniel Creegan, Emily Glynn, Bryan T. Hennessy, Patrick G. Morris, William Grogan, Oscar S. Breathnach
Journal: Journal of Clinical Oncology (2020)

e24187 Background: Systemic treatments can improve symptom burden and prolong life in patients with advanced cancer. However, these therapies come with associated toxicities and in some cases can result in reduced quality of life for patients with no possibility of cure. International data has suggested that this cohort of patients have a poor understanding surrounding the goals of treatment in the advanced disease setting. We aimed to evaluate the expectations for cure and palliation from systemic therapies among patients with advanced, incurable cancer in our institution. Methods: Patients on active treatment attending the Oncology Day Ward completed anonymous questionnaires over a four week period. Personal demographics, decision making for treatment and expectation of benefit and toxicity was assessed. Analysis was carried out on patients assessed to have advanced metastatic disease. Results: 254 patients completed the questionnaire. 217 patients were assessed to have metastatic/incurable disease based on responses. 57% were male, 56% were age 30-64 and 35% had completed university level education. 42% of patients stated that treatment was very likely or somewhat likely to cure their cancer. Among patients who reported that a cure was very likely, there were more men (62%) compared to women (38%), more patients were aged less than 65 (62%) compared to over 65 (38%) and more patients had only completed elementary school level education (71%) compared to university level education (29%). Most patients (84%) felt treatment was either very likely or somewhat likely to help them live longer. 68% of patients felt treatment would help them with problems related to their cancer and 33% of patients felt that treatment was very likely to have side effects or complications. 22% of patients stated that doctors made decisions without their input. Conclusions: Many patients receiving treatment for incurable cancers do not understand that it is unlikely to be curative. Male gender, younger age and a lower level of education appears to be associated with unrealistic expectations. This could compromise their ability to make informed treatment decisions. More effective communication around goals of treatment and end of life care may help to improve patients understanding and expectations around the outcomes of chemotherapy.
Impact of proteasome inhibitor vs. IMiD maintenance therapy on outcomes of patients with high-risk multiple myeloma (HRMM).
Authors: Eric Leon Tam, David Joseph Iberri, Michaela Liedtke, Lori S. Muffly, Parveen Shiraz, Matthew Joshua Frank, Robert Lowsky, Andrew Rezvani, Robert Negrin, Everett Meyer, Sally Arai, Laura J. Johnston, Judith Shizuru, Wen-Kai Weng, David Bernard Miklos, Surbhi Sidana
Journal: Journal of Clinical Oncology (2020)

e20557 Background: The ideal choice of maintenance therapy in patients with HRMM high-risk multiple myeloma remains unknown. We analyzed the outcomes of patients with HRMM undergoing transplant receiving different maintenance approaches. Methods: Patients with MM undergoing their first ASCT from 2012-19 within 1 year of diagnosis were identified from the prospectively maintained database of patients undergoing ASCT. HRMM was defined as having t(4;14), t(14;16), t(14;20), del17p13, or gain 1q detected on fluorescent in situ hybridization (FISH). Results: Of the 412 patients undergoing ASCT within 1 year of diagnosis, 333 had FISH data available and of these, 37% (124/333) patients had high-risk cytogenetics. Distribution of HR cytogenetics was as follows: deletion 17p: 37% (n = 46), t(4;14): 27% (n = 34), t(14;16) or t(14;20): 12% (n = 26), gain1q: 31% (n = 41). 9% (n = 12) had more than one HR abnormality. In patients with HRMM, median age at transplant was 59 years (range: 39 to 73), and 61% (n = 103) were males. 64% (n = 107) of high-risk patients received post-transplant maintenance therapy. Maintenance therapy in this group included a proteasome inhibitor (PI) in 34% (n = 29), immunomodulatory drug (IMiD) in 59% (n = 51), or both in 7% (n = 6). There was no difference in baseline characteristics of HRMM patients receiving PI vs. IMiD maintenance, except that patients with del17p were more likely to receive PI maintenance therapy (55% vs 28%, p = 0.01). (Table) After a median follow-up of 3.1 years from diagnosis, patients with HRMM had inferior PFS compared to patients with standard risk disease, with median PFS of 3 vs. 4.8 years, p &lt; 0.001. Amongst the 86 HRMM patients receiving maintenance therapy, median PFS in patients receiving PI vs. IMiD vs. both PI + IMiD maintenance was 3 vs. 3.2 vs. 2.2 years, respectively, log-rank p = 0.7. In the sub-group of patients with 17p deletion, median PFS in the three groups was 3 vs. 2.9 vs. 2.2 years, respectively, log-rank p = 0.7. Conclusions: Patients with HRMM have inferior PFS compared to patients with standard risk disease. We observed similar outcomes in HRMM patients post-transplant regardless of the choice of maintenance therapy. [Table: see text]
Clinical characters of somatic DNA damage repair (DDR) gene mutations in Chinese NSCLC patients.
Authors: Ke Ma, Hao Rong, Changbin Zhu, Huachuan Zhang, Jintao He, Bo Xiao, Jiang Zhu, Jun Peng
Journal: Journal of Clinical Oncology (2020)

e13665 Background: Chinese NSCLC patients displayed unique genetic profile. NSCLC patients with DNA damage repair gene mutations showed distinct clinical appearance as well as superior response to immunotherapy. This study aims to disclose distribution of DNA damage mutations as well as their clinical characters in Chinese NSCLC patients. Methods: One hundred and ten patients with pathologically confirmed NSCLC were consecutively recruited from 2016-2018 in our center. Genomic DNA was captured and sequenced for 508 cancer related genes by BGI-seq 500. Raw data was processed followed by variant calling via in-house developed pipeline. Results: 89 (of 110) patients with median age of 55 years old (33-74 years) were included into final analysis due to complete follow-up as well as sufficient FFPE tissue for successful genomic profiling. Among them, 12 patients were squamous NSCLC, 72 patients were non-squamous NSCLC. Among 89 patients, 22 patients (24.7%) carried 36 mutations in 21 DDR genes (BRCA2 n = 6, BAP1 n = 3, ARID1A n = 2, ATM n = 2, ATR n = 2, BLM n = 2, FANCF n = 2, PARP1 n = 2,BARD1 n = 1,BRCA1 n = 1,CHEK2 n = 1, FANCD2 n = 1,FANCE n = 1,FANCG n = 1,FANCM N = 1,NBN n = 1,PARP3 n = 1,POLQ n = 1,RAD50 n = 1,RAD51C n = 1), most of them belongs to homologous recombination repair pathway (n = 19, 21.34%).8 patients carried compound mutations in DDR genes. No difference was found in age of initial diagnosis between DDR mutated and DDR wild type patients. While, ever smokers (RR (95%CI): 2.12 (1.37-3.20),P = 0.003), squamous NSCLC (RR(95%CI):4.47 (1.62-12.03), P = 0.006), male (RR (95%CI): 1.77(1.23-2.44),P = 0.006) displayed significantly higher prevalence of DDR gene mutations. Only one stage I patient carried DDR mutation(P = 0.008). Conclusions: In this study, mutation spectrum of DDR genes was proposed in Chinese NSCLC patients. DDR gene mutations more possibly occurred in male, higher disease stage as well as in squamous NSCLC and smokers. These findings show potential relevance to disease prognosis which needs further investigation.
Immune checkpoint inhibitor in nasopharyngeal carcinoma: Multi-institution experience.
Authors: Jong Chul Park, Lori J. Wirth, John R Clark, Julia Durbeck, Won Jin Ho, Karim Boudadi, Hyunseok Kang
Journal: Journal of Clinical Oncology (2020)

6538 Background: The current standard treatment for unresectable recurrent/metastatic (R/M) nasopharyngeal carcinoma (NPC) is cytotoxic chemotherapy but prognosis remains poor. Recent phase I-II trials of anti-PD-1 therapy (aPD-1) have demonstrated promising activity in R/M NPC, but the published experience is primarily limited to Epstein-Barr virus (EBV) positive tumors in the Asian population. Here we report our three institutional real-world experience with aPD-1 in patients (pts) with R/M NPC. Methods: A retrospective analysis was conducted after IRB approval at the Massachusetts General, Johns Hopkins, and University California San Francisco Hospitals. Demographic and clinical data was collected on pts with R/M NPC who received aPD-1 at the participating institutions. Objective response rate (ORR) was the primary outcome of interest and progression free survival (PFS) and overall survival were secondary outcomes. Univariate and multivariate analyses were conducted to assess association between clinicopathologic factors and outcomes, using logistic regression models. Results: A total of 36 pts were identified: 20 pts were treated with pembrolizumab and 16 with nivolumab. Median age was 50 (15-74). Twenty-nine (81%) were male. Twenty pts (56%) were Asian. Twenty-nine pts (81%) had EBV positive disease. Nine (25%) had aPD-1 as first-line therapy (1L). Molecular profiling results were available in 16 pts: TP53 mutation was the most common alteration (25%) and was limited to EBV negative tumors. Median total mutational burden (TMB) was 3/Mb (1-28). Median PD-L1 expression was 10% (0-90). Median follow up was 13.9 months (mos). Objective response was evaluable in all 36 pts: 9 pts achieved objective response (ORR 25.0%, 95% CI 12.1-42.2) with 2 complete responses: EBV positive vs. negative (27.6% vs. 14.2%, P=0.472), Asian vs. non-Asian (25% vs. 25%, P=1.000), and 1L vs. &gt;1L (33.3% vs. 22.2%, P=0.511). Thirteen pts had stable disease (disease control rate 61.1%). Responses were seen in both TMB high (28/Mb) and low (1/Mb) tumors and no association with PD-L1 expression was observed. One-year survival rate was 81.3%. EBV positive pts had a trend towards better survival (84.8 vs. 66.7, P=0.640). Median PFS was 5.5 mos and not different between EBV positive vs. negative pts (5.6 vs. 4.0 mos, P=0.919). Conclusions: Our multi-institutional real-world experience with checkpoint inhibitor therapy in R/M NPC confirms that a similar degree of activity is seen as reported in the phase I-II experience in diverse races, but efficacy seems more prominent in EBV positive disease.
Safety and efficacy of neoadjuvant intravesical oncolytic MV-NIS in patients undergoing radical cystectomy (RC) for urothelial carcinoma but ineligible for neoadjuvant cisplatin-based chemotherapy.
Authors: Bradley C. Leibovich, Tanner Miest, Paul R Young, Mark L. Gonzalgo, Stephen A. Boorjian, Matthew K. Tollefson, R. Jeffrey Karnes, Igor Frank, Timothy D. Lyon, Tessa Kroeninger, Shruthi Naik, Monica Reckner, Rosa M Diaz, Stephen Kaesshaefer, Ena Whitelaw, Bethany A Brunton, Alysha Newsom, Nandakumar Packiriswamy, Kah Whye Peng, Alice Susannah Bexon
Journal: Journal of Clinical Oncology (2020)

TPS3172 Background: Bladder cancer is a leading cause of cancer death in the United States. Over 90% of bladder cancer cases are urothelial carcinomas (UC) that may present as a non-muscle-invasive (NMIBC) or muscle-invasive disease (MIBC). Standard of care for NMIBC includes transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and immunotherapy with Bacillus Calmette-Guerin (BCG). Patients (pts) with high-grade BCG-refractory NMIBC or MIBC undergo RC, which involves complete bladder removal and pelvic lymphadenectomy. RC severely impacts quality of life with significant morbidity. Oncolytic viruses are showing promise in UC, and MV-NIS has proven efficacy in other tumor types. MV-NIS is an investigational oncolytic measles virus with an excellent safety profile, irrespective of route of administration (n &gt; 100). MV-NIS-related adverse events are limited to infusion reactions and transient CBC changes, and little local toxicity is anticipated with intravesical therapy. Clinical efficacy of this oncolytic may be related to absence of measles immunity. Based on this, the clinical strategy for MV-NIS is focused on targeting immune-privileged sites via intra-tumoral or intravesical routes, alone or in combination with checkpoint inhibitors. We hypothesize that intravesical therapy with oncolytic MV-NIS can improve clinical outcomes for (a) BCG refractory NMIBC pts to avoid or delay the need for RC; and (b) MIBC pts undergoing RC. Methods: This study is enrolling pts undergoing RC who are ineligible to receive neoadjuvant chemotherapy. The trial has 2 stages to (a) determine the safety and tolerability of intravesical MV-NIS, and (b) assess preliminary efficacy. Part (a) includes 4-24 pts in a timing cohort with doses administered at increasing durations (1-4 weeks) prior to RC to establish safety of a single MV-NIS dose. Part (b) includes an expansion cohort (n = 12) to evaluate the safety and efficacy of 2 intravesical doses of MV-NIS at 2-week intervals prior to RC. Safety is assessed using NCI-CTCAE V5 and Clavien-Dindo grading of operative complications. The efficacy endpoint is pathologic stage at time of RC (pT0 rate), which can be compared to pre-study TURBT stage. Additional exploratory studies include PK and PD analyses in urine, blood and tumor. Enrollment is ongoing at 2 Mayo Clinic sites (Rochester, MN and Jacksonville, FL) and the study has now progressed from the timing cohort into the expansion cohort. Clinical trial information: NCT03171493 .
Exercise therapy for hypertensive patients with diabetes mellitus
Authors: Fangrong Jiang, Dajin Liu, Yongmei Kong
Journal: BMJ (2018)

There is a synergistic effect of hypertension combined with diabetes to cardiovascular risk. The blood pressure control is more difficult for hypertensive patients complicated with diabetes, leading to aggravating the vital organs damage (such as heart, brain, kidney). Therefore, blood pressure and blood glucose levels should be simultaneously and effectively controlled. The exercise therapy not only eliminates the risk factors for cardiovascular disease, but also lowers blood pressure and blood sugar, resulting in the reduction of cardiovascular mortality and all-cause mortality. This article reviews the effects of exercise therapy on blood pressure and blood glucose, and provides guidance for hypertensive patients with diabetes mellitus.


Key words: 
Hypertension; Diabetes mellitus; Exercise therapy
Expression level of ACE2 in lung adenocarcinoma.
Authors: Danni Liu, Tianhao Mu, Shifu Chen
Journal: Journal of Clinical Oncology (2020)

e21022 Background: 2019-nCoV, a novel coronavirus (2019-nCoV), has infected tens of thousands of people in Wuhan, Hubei Province, China. This new coronavirus has led to hundreds of deaths, and especially threatened people with underlying diseases. ACE2 was reported as the 2019-nCoV putative receptor. The expression abundance of ACE2 may cause different disease progressions. Here, we evaluated the expression profile of ACE2 from 283 samples in lung adenocarcinoma . Methods: 283 samples from the public datasets (GEO: GSE31210 and GEO: GSE2109) were grouped by tissue, ethnicity and gender. The data was normalized by the RMA algorithm. Student 's t-test was used to compare the expression of ACE2 in different groups . Results: The expression level of ACE2 of primary lung tumor was significantly higher than normal lung tissue ( p &lt; 0.0001). ACE2 was significantly differential-expressed between Asian and Caucasian lung adenocarcinoma patients ( p &lt; 0.0001). However, no significant difference of the expression of ACE2 was observed by gender ( p = 0.33). Conclusions: ACE2 was highly expressed in primary lung adenocarcinoma , compared with normal lung tissues. The expression level of ACE2 was higher in Asian lung adenocarcinoma patients than Caucasian’s. These conclusions imply that Asian people with lung adenocarcinoma may be more vulnerable to 2019-nCoV.
两户家庭内严重急性呼吸综合征传播和治愈后心理咨询
Authors: 彭荣立, 赵林, 陈朋曲, 左惠军
Journal: BMJ (2004)

社区访视对做好严重急性呼吸综合征(SARS)治愈患者出院后的社区医学观察和心理咨询十分必要. 1.资料与方法:安贞社区24号楼共有3户家庭出现6名确诊SASR患者,其中2户为家庭间传播,1户为医院交叉感染.家庭间传播的602室有老少三代共5人,年龄8～69岁,年龄69岁的男性最先发病,且因确诊较晚,患有糖尿病而死亡.其家庭中4人在其患病1周后也先后发病,仅孙子幸免.
HLA genotyping in synovial sarcoma: Identifying HLA-A*02 and its association with clinical outcome.
Authors: Evan Rosenbaum, Kenneth Seier, Chaitanya Bandlamudi, Ping Chi, Mark Andrew Dickson, Mrinal M. Gounder, Ciara Marie Kelly, Mary Louise Keohan, Sujana Movva, Benjamin Nacev, Emily Kanaya Slotkin, Noemi Simeone, Mark Donoghue, Li-Xuan Qin, Cristina R. Antonescu, William D. Tap, Sandra P. D'Angelo
Journal: Journal of Clinical Oncology (2020)

e23560 Background: Patients (pts) with synovial sarcoma (SS) and an HLA-A*02 genotype whose tumors express NY-ESO-1 may be eligible for clinical trials of adoptive T cell therapy. We reasoned that a next generation tumor sequencing platform utilizing matched normal DNA (MSK-IMPACT) could accurately identify HLA genotype. Although HLA-A*02 is necessary for some adoptive T cell therapies, the prognosis of this genotype on clinical outcome has not been described in SS. Methods: Pts with metastatic SS who consented to screen for a clinical trial of engineered T cells had high-resolution HLA genotyping performed with a Clinical Laboratory Improvement Amendments (CLIA)-certified test. Where feasible, HLA genotype and loss-of-heterozygosity (LOH) of HLA alleles were determined from IMPACT samples. Overall survival (OS) was estimated in three overlapping cohorts and stratified by HLA-A*02 status: pts treated with anthracyclines or alkylators in the first line, pazopanib in the second line or beyond, and all pts from time of metastasis. Results: 66 pts with SS were screened, but not treated with T cells; 30% (n = 20) were HLA-A*02-positive on a CLIA-certified outside test. 23 pts had HLA genotyping both by IMPACT and an outside laboratory, 22 (96%) of whom had concordant results. 3 pts had LOH of at least 1 HLA allele, including one with LOH of HLA*02:01 in the primary tumor. Among pts treated chemotherapy (n = 36) or pazopanib (n = 37), OS did not significantly differ between HLA-A*02-positive or negative pts. Univariable analyses of OS from the time of metastasis in the whole cohort identified primary tumor size and time to metastasis as variables significantly associated with outcome (hazard ratio (HR) 1.2, 95% confidence interval (CI) 1.123 – 1.345 [P &lt; 0.001] and HR 0.99, 95% CI 0.976 – 0.999 [P = 0.032], respectively). HLA-A*02-positive status and age did not reach the significance threshold (HR 1.95, 95% CI 0.995 – 3.813 [P = 0.052] and HR 1.021, 95% CI 0.999 – 1.044 [P = 0.061], respectively). Multivariable analysis found older age and larger tumor size were independently associated with significantly shorter OS (HR 1.03, 95% CI 1.002 – 1.049 [P = 0.037] and HR 1.2, 95% CI 1.127 – 1.37 [P &lt; 0.001], respectively). Conclusions: Targeted exome panels like IMPACT that utilize matched tumor-normal DNA may accurately identify HLA genotype. Detection of LOH at HLA loci may identify a subgroup of pts who would be refractory to treatment with HLA-A*02-restricted engineered T cells. HLA-A*02 status was not associated with a statistically significant survival difference in pts with metastatic SS.
Real-world effectiveness of nab-paclitaxel plus carboplatin as first-line therapy for patients with advanced NSCLC: Results of the second interim analysis of the NEPTUN study.
Authors: Tobias Nicolaas Dechow, Jorge Riera-Knorrenschild, Björn Hackanson, Ludwig Fischer von Weikersthal, Holger Schulz, Marco Chiabudini, Barbara Timm, Ralf Zerbes, Karin Potthoff
Journal: Journal of Clinical Oncology (2020)

e21611 Background: Collecting real-world evidence is required not only to evaluate effectiveness and safety in routine clinical practice, but to improve clinical cancer outcomes. Methods: NEPTUN is a prospective, multicenter, non-interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of first-line nab-Paclitaxel plus carboplatin in patients (pts) with advanced or metastatic non-small cell lung carcinoma (NSCLC) in the real-world setting in Germany. The primary endpoint was 6-months progression free survival rate (PFSR). Descriptive statistics were used to analyze data. Results: Between August 2016 and June 2019, 408 pts were enrolled at 75 active sites, 373 pts started treatment according to label. The cut-off date for this interim analysis (07 Dec 2019) was after all pts were observed for at least 6 months. The 6-months PFSR was 40.8% (95% CI, 35.3-46.2), median PFS 5.2 months (95% CI, 4.5-5.7). Overall response rate was 41.5% (95% CI, 36.3-46.8) with a complete response documented in 6 pts (1.7%) and a partial response in 142 pts (39.8%). Disease control rate was 61.6% (95% CI, 56.4-66.7). Employing a multivariable cox regression model for PFS adjusted for ECOG, histology, age group, renal impairment, and smoking status, elderly patients and patients with squamous histology were identified as being of favorable risk (HR squamous vs. non-squamous histology 0.76 (95% CI, 0.58-1.01); HR for ≥70 vs. &lt; 70 years of age 0.80 (95% CI, 0.59-1.08)). Median overall survival (OS) was 10.5 months (95% CI, 9.2-11.6) with 9.6 months (95% CI, 7.7-11.2) for non-squamous and 11.8 months (95% CI, 9.2-13.8) for squamous histology. 12-months OS rate was 43.1% (95% CI, 37.3-48.7). The most common treatment-emergent AEs (TEAEs) were anemia (26.5%), leukopenia (25.7%) and thrombocytopenia (16.6%). Polyneuropathy was documented for 11.3% of pts. 54.2% of pts developed TEAE grade 3/4 including leukopenia (10.2%), anemia (8.6%) and pneumonia (5.1%). 9.9% pts discontinued nab-paclitaxel due to nab-paclitaxel-related TEAEs. EQ-5D-5L visual analogue scale and FACT-L total score remained stable during therapy. Conclusions: nab-Paclitaxel plus carboplatin given first-line according to German SmPC in advanced NSCLC patients in a real-world clinical setting is an effective and safe therapy commonly applied. These results were similar to those reported in the phase iii clinical trial setting. QoL scores remained stable during first-line treatment. No new safety signals emerged. Clinical trial information: NCT02799862.