tbuckley/cabot-search huggingface dataset:
Radiation therapy following breast conserving surgery (BCS) in women with early-stage breast cancer and low oncotype scores.
Authors: Nicholas Damico, Michael Kharouta, Janice A. Lyons, Eleanor Elizabeth Harris
Journal: Journal of Clinical Oncology (2020)

e12547 Background: Clinical trials have demonstrated radiation therapy (RT) significantly reduces local recurrence following BCS, but that omission of RT does not compromise survival in the majority of women with early stage, low risk breast cancer. Criteria for omission of RT have been based on clinical factors such as age, stage, tumor size, surgical margins and estrogen receptor (ER) status. The utility of Oncotype DX RS in determining benefit of RT is not well defined. Methods: The National Cancer Database (NCDB) was queried for women ages 50-69 with T1N0M0, grade 1-2, ER+, Her2- breast cancer who underwent BCS with negative margins and had Oncotype DX RS of 0-18. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between patients who received RT and endocrine therapy (ET) versus ET alone using logrank analysis. Propensity matching was performed to reduce the impact of potential confounders and balance sample bias. Cox proportional hazards regression was used to identify predictors of OS. Results: A total of 13,648 women met inclusion criteria. The median age was 60 years. 13,389 women had adjuvant RT+ET, while 259 women had ET alone. Five year OS was 98.6% in patients who underwent RT+ET compared to 95.5% in those that had ET alone (p = 0.0012). Propensity-matching by age, Charlson Deyo Comorbid Condition score, tumor size, Oncotype RS, and race. Five year OS in the propensity matched cohort was 99.6% for women receiving RT+ET, and 98.3% for ET alone, which was not significantly different (p = 0.095). On multivariate analysis receipt of radiotherapy was not predictive of survival. Age and comorbidity score were the only significant predictors of survival. Conclusions: Patients who receive adjuvant RT with low risk, early stage ER+/Her2- breast cancer had higher OS than women who received ET alone on univariate analysis. However, results from both multivariate analysis and propensity score matching suggest no survival benefit to the addition of RT. Prospective studies are underway assessing omission of RT on the basis of multigene assays rather than clinical features alone. [Table: see text]
Breast cancer in women aged 80 years and older: Clinical characteristics and treatment patterns according to biologic subtype.
Authors: Stephanie M Wong, Jean-Francois Boileau, Mariam Rana, Thierry Muanza, Richard G. Margolese, Johanne Monette, Boris Bahoric, Mark Basik
Journal: Journal of Clinical Oncology (2020)

e12594 Background: Older age is associated with poorer breast cancer-specific survival (BCSS) outcomes, despite a higher prevalence of biologically favorable disease. We sought to evaluate differences in the clinical characteristics and management of older women according to biologic subtype of breast cancer. Methods: The Surveillance, Epidemiology, and End Results (SEER) treatment database was queried to identify all women aged 80 years or older with a first diagnosis of invasive breast cancer between 2010 and 2016. Patients were subgrouped according to biologic subtype and clinical and treatment-related variables were compared. Multivariable logistic regression was then performed to determine factors independently associated with receipt of breast-conserving surgery (BCS) and adjuvant radiation. Results: Overall, 27,375 women with a median age of 84 (range, 80-108 years) met inclusion criteria. The majority of older women were diagnosed with HR+HER2- breast cancer (78.9%), followed by HER2+ (11.0%) and triple-negative breast cancer (TNBC) (10.0%). In women with stage I-III disease, non-operative management was employed in 13.4% of HR+HER2- patients, compared to 16.7% of HER2+ patients and 11.0% of TNBC (p &lt; 0.001). In those undergoing surgery, BCS was most common in HR+HER2- patients (80.9%), compared to HER2+ (68.9%) and TNBC (67.8%; p &lt; 0.001). Axillary surgery was performed in 74.0% of early stage patients with HR+HER2- disease, compared to patients with HER2+ (77.8%) and TNBC (79.3%; p &lt; 0.001). In adjusted analyses controlling for stage and clinical variables, women aged 80 years or older with HER2+ breast cancer and TNBC had a lower likelihood of BCS (OR HER2+ 0.72, 95% CI 0.65-0.80; OR TNBC 0.72, 95% CI 0.65-0.81), and an increased likelihood of adjuvant radiation (OR HER2+ 1.14, 95% CI 1.02-1.27; OR TNBC 1.40, 95% CI 1.25-1.57). Conclusions: One fifth of women with breast cancer over age 80 are diagnosed with HER2+ and triple-negative subtypes, which are associated with more aggressive local therapy. Further studies are warranted to determine if higher rates of adjuvant radiation optimize local control in older HER2+ and TNBC patients at increased risk for early locoregional recurrences.
YsRNA aberrant expression in colorectal cancer patients.
Authors: Inna A. Novikova, Denis S. Kutilin, Natalya N. Timoshkina, Sergey I. Poluektov, Roman E. Tolmakh, Andrey V. Dashkov, Dmitry Haragezov, Evgeniy N. Kolesnikov, Vladimir A. Dontsov, Natalya V. Soldatkina, Dmitry S. Petrov, Yuriy A. Gevorkyan, Oleg Ivanovich Kit
Journal: Journal of Clinical Oncology (2020)

e13525 Background: Cancer is a disease characterized by uncontrolled cell proliferation. DNA replication is the main driving force behind cell proliferation in both normal development and cancer. Non-coding Y-RNAs are important factors in initiating DNA replication in the nuclei of human cells. Excessive expression of Y-RNA is characteristic of tumors of the bladder, cervix, kidney, lung and prostate. It has also been shown that the level of small RNAs formed from the 3'- and 5'-ends of Y-RNA is significantly higher in patients with certain types of cancer compared to healthy people, therefore, these RNAs may have diagnostic value. However, for colon tumors, data on the expression of Y-RNA/YsRNA obtained in previous studies are ambiguous. The aim of the study was to analyze the differential expression of YsRNA in the tumor and non-tumor tissue of patients with CRC using next generation sequencing (NGS). Methods: For NGS, 10 patients with CRC (colon adenocarcinoma, G2). were selected. Small RNA fractions were isolated using the mirVana miRNA Isolation Kit protocol (Ambion, Life Science Technologies, USA). The library was prepared for sequencing using the TruSeq Small RNASample Preparation Kit (Illumina, USA). Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The determination of the copy number of Y-RNA fragments (YsRNA, 19-34 bp) was carried out by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences presented in the databases. In the analysis of differential expression, the edgeR method, implemented in the R language, was used. Results: Several different fractions of YsRNA were detected in tumor and non-tumor tissues: hY3sRNA (the most represented fraction, more than 70%), hY5sRNA and hY1sRNA. In tumor tissue relatively non-tumor, a statistically significant (p &lt; 0.001) increase of 4 and 6 times the number of copies of hY3sRNA and hY5sRNA, respectively, was detected. The function of YsRNA in tumor and normal cells has not yet been established. Conclusions: Thus, in the tumor colon tissue differential expression of 2 YsRNA fractions - hY3sRNA and hY5sRNA, was detected. These YsRNAs can become promising tumor markers and targets for the treatment of CRC, as well as make certain contributions to understanding the mechanisms of carcinogenesis in this nosology.
The effect on financial toxicity and well-being of cancer trial patients through the reimbursement of ancillary costs by the lazarex care program (LCP).
Authors: Dana Dornsife, Robert G. Johnson
Journal: Journal of Clinical Oncology (2020)

e19030 Background: Financial toxicity is a significant issue for many cancer patients (pts) and an even greater concern for pts considering a cancer clinical trial (CT) given the potential issues of distance to the trial site, additional trips to the cancer center, etc. Lazarex Cancer Foundation (LCF) has developed an efficient mechanism to quickly evaluate pts who are economically challenged and often underserved and to efficiently reimburse the non-clinical expenses (i.e. travel, lodging). Reimbursement (RI) of ancillary CT expenses can help to remove this important barrier and effect CT enrollment, retention, and diversity. Methods: Data was retrospectively reviewed from the LCP for years 2015 to 2019, and assessed for age, gender, race/ethnicity, household income (HI), type of assistance, and compared with trends from the prior 5 years. In addition, information was obtained concerning whether the RI was an important determinant in the decision to enroll or remain enrolled, the impact of RI on the pts’ well-being, and the ease/difficulty of the application and RI process. Results: During this period, 2,911 pts were approved for RI: 45% male, 55% female; 12.2% Latino/Hispanic, 7.6% black/African-American, 3.8% Asian/Pacific Islander, 72% white, and 4.3% multi-ethnic/other. The median HI was $35,000-$49,000 with 32% of the HI at less than $25,000, and 17% less than $15,000. RI expenses were distributed: 37% airfare, 37% lodging, and 26% ground transportation. There were increases in the % of minority pts and decreases in the median HI when compared with the five years prior. Questionnaires with 65% return rate of active pts indicated that 38% of pts stated that RI contributed to their positive CT decision, 92% of pts indicated RI had a significant impact (moderate to extremely high) on their sense of well-being with 82% in the high to extremely high category. 96% reported the application as not difficult to easy and only 4% noted the RI process itself as difficult. Conclusions: Accumulating data indicates that the socioeconomic financial toxicities are a significant root cause of inequitable access to CT. RI for pts upon whom the costs of participation place an undue burden, decreases their vulnerability, increases their well-being, and helps protect their rights to equal treatment. The LCF with more than ten years of experience with pt RI is currently expanding its efforts into targeted major cancer centers where all eligible pts will be enabled: the IMPACT (Improving Patient Access to Cancer Clinical Trials) Program.
Evaluation of empathy level of general practitioners in a general hospital and its related factors
Authors: Ruihong Liu, Lujuan Lin, Zhaozhang Feng, Hanji Wu, Yizhen Jia, Zhuo Li, Zhiwei Huang
Journal: BMJ (2017)

Objective
To assess the empathy level of general practitioners (GPs) in the outpatient clinics of a general hospital, and to investigate the related factors.


Methods
Patients attending the Family Medicine Clinic of HKU-Shenzhen Hospital in September 2014 and met the inclusion criteria were asked to complete the questionnaire which included general characteristics, overall satisfaction and the Measure-Consultation and Relational Empathy Measure (CARE) Scale after the consultation.


Results
Of the 1 818 questionnaires retrieved, 1 690 CARE scales were completed (intact rate was 92.96%). The overall satisfaction rate was 95.92% (1 621/1 690). And 97.28% (1 644/1 690) of the patients would recommend family medicine service to their friends or relatives. The total score of CARE scale was (45.47±6.26), and the scores of 4 CARE components were (4.63 ± 0.59), (4.43 ± 0.81), (4.54 ± 0.69) and (4.55 ± 0.66), which showed significant difference (P<0.01). The multivariate linear regression analysis showed that the mean CARE scores were not influenced by gender and education levels of the patients, gender of the consulting doctors, initial/follow up consultation, and the location of the consultation. The mean CARE scores were influenced by age of patients and the reasons for consulting (P<0.05). There was a moderate correlation of the CARE scores with the overall satisfaction of patients (r=0.613, P<0.001) and patient′s recommendation of the clinic (r=0.466, P<0.001).


Conclusion
Doctors who were evaluated in this study have a higher empathy level than results from other countries. There is positive correlation between doctor′s empathy level and patient′s overall satisfaction. The result of doctor′s empathy level may be influenced by patient′s age and the reasons for consulting.


Key words: 
Empathy; Questionnaire; General practitioners
Comparison of two subcutaneous insulin regimens in type 2 diabetic patients with fractures during perioperative period
Authors: Wei Deng, Li-nong Ji, Bo-song Zhang, Guo-ying Zhang, Li-li Huo
Journal: BMJ (2009)

We compare the results of two subcutaneous insulin regimens in type 2 diabetic patients with fractures during the perioperative period. In group Ⅰ 162 patients received regular insulin three times+ NPH insulin bedtime protocol; in group Ⅱ 72 patients received regular insulin three times + NPH insulin twice protocol. The difference of the time achieving satisfactory level of blood glucose (BG) and associated factors were analyzed, and the related complications were observed. The average time achieving satisfactory BG level was (9.1±3. 3) days and (7.0±2.6) days for group Ⅰ and Ⅱ respectively (P <0.05). There were no statistical differences in hypoglycemia, infection and thrombosis between two groups. Binary logistics regression showed that the time of achieving desired BG level was associated with blood glucose(BG) and the proportion of the regular insulin and the NPH. The results indicate that five times insulin injection method can shorten the time of achieving desired BG level and may be benefit to diabetic patients with fracture.

Key words: 
Diabetes mellitus;  Intraoperative period
Efficacy of rituximab in treatment of children with refractory idiopathic thrombocytopenic purpura
Authors: Yu-fang Yuan, Wen-xia Kuai, Xiao-chun Yang
Journal: BMJ (2012)

Fifty children with refractory idiopathic thrombocytopenic purpura (RITP) were treated with rituximab (n =26) or vincristine (n =24).The response rate,adverse reaction and recurrence rate in two groups were compared.The CD19 +/CD20 + B cells in peripheral blood were detected by flow cytometry in 26 patients before and after RITP treatment.The response rates of rituximab group was significantly higher than that of vincristine group ( 69.2％ vs. 37.5％,x2 =9.74,P ＜ 0.01 ). There was no significant difference in the rate of adverse reaction between two groups ( 11.5％ vs.8.3％,x2 =0.62,P ＞ 0.05 ).The recurrence rate of rituximab group ( 22.2％ ) was significantly lower than that of vincristine group (55.6％,x2 =7.24,P ＜ 0.05 ).In rituximab group the platelet count after treatment was significantly higher than that before treatment ( t =12.48,P ＜0.01 ),and the ratio of CD19 +/CD20 + B cells decreased significantly after treatment compare to that before treatment ( t =6.71,P ＜0.05 ).Rituximab is effective in treatment of refractory idiopathic thrombocytopenic purpura in children,which may be associated with decreased B cells in peripheral bloos.

Key words: 
Purpura, thrombocytopenic, idiopathic; Child
Metastatic lymph node ratio as better prognostic tool than TNM system in colorectal cancer.
Authors: Filipa Macedo, Hugo Sequeira, Katia Ladeira, Nuno Bonito, Charlene Viana, Sandra Martins
Journal: Journal of Clinical Oncology (2020)

e16128 Background: Colorectal cancer (CRC) is the third leading cause of cancer death in the world. Lymph node metastasis is an important prognostic factor; however, the minimum number of lymph nodes that should be evaluated for adequately categorizing lymph node status is still a controversial theme. The TNM staging system has limitations in defining the pN category. The lymph node ratio (LNR) may be a better prognostic indicator. Objectives: Evaluate the impact on the prognosis of patients operated for CRC, comparing the LNR with the pN category of TNM system. Methods: We studied 1065 patients treated at a General Surgery Department from 01/01/2000 to 08/31/2012. The LNR was separated into 5 categories based on three previously calculated cut-off values: LNR0 (0), LNR1 (0.01-0.17), LNR2 (0.18- 0.41), LNR3 (0.42-0.69) and LNR4 (≥0.70). Results: The results of the univariate analysis indicated significant differences in survival according to age (p &lt; 0.001), tumor size (p &lt; 0.001), serosal invasion (p &lt; 0.001), histological type (p = 0.002), differentiation (p &lt; 0.001), pT (p &lt; 0.001), pN (p &lt; 0.001), LNR (p &lt; 0.001), M (p = 0.001), TNM stage (p &lt; 0.001), venous invasion (p &lt; 0.001). Multivariate analysis confirmed the LRN, pN, age, venous invasion and pT as independent prognostic factors. The survival analysis showed significant differences between the categories of pN (p &lt; .001) and LNR (p &lt; .001). Spearman correlation analysis showed a significant correlation between the total number of dissected lymph nodes and the number of metastatic lymph nodes (rs = 0.167, p &lt; 0.001). The total number of dissected lymph nodes is not significantly correlated with LNR (rs = -0.019, p = 0.550). Conclusions: In this study LNR seems to demonstrate a superior prognostic value when compared to the pN categories, in part due to its greater independence regarding the extent of lymphadenectomy.
Colibactin DNA-damage signature indicates mutational impact in colorectal cancer
Authors: Paulina J. Dziubańska-Kusibab, Hilmar Berger, Federica Battistini, Britta A. M. Bouwman, Amina Iftekhar, Riku Katainen, Tatiana Cajuso, Nicola Crosetto, Modesto Orozco, Lauri A. Aaltonen, Thomas F. Meyer
Journal: Nature Medicine (2020)
Clinical implications of loss of minimal residual disease (MRD) negativity in multiple myeloma.
Authors: Meera Mohan, naveen kumar yarlagadda, Dinesh Atwal, Yadav Pandey, Arya Roy, Richa Parikh, James Lopez, Sharmilan Thanendrarajan, Carolina D. Schinke, Daisy Alapat, Frits Van Rhee, Samantha Kendrick, Maurizio Zangari
Journal: Journal of Clinical Oncology (2020)

8514 Background: Attainment of MRD negativity in multiple myeloma (MM) patients is increasingly considered an optimal therapeutic endpoint, but little is known about the MRD evolution in those who achieve this milestone. We investigated the clinical implication of loss of MRD negativity or MRD conversion in patients with ≥VGPR. Methods: We identified and followed 606 patients achieving a sustained ≥VGPR with bone marrow MRD negativity(≥ 2 consecutive reading) following treatment on a total therapy protocol and with a median follow-up of 10 y. All patient had negative PET and MRI DWIBS at enrollment. Serial BM aspirate MRD was determined by 8-color next generation flow (NGF, EuroFlow) with a minimal sensitivity of 10 −5 cells. Results: Most MM patients were considered low risk with a UAMS GEP70 score of ≤ 0.66 (92%; 495/538) . While 60% (364/606) of patients had sustained MRD negativity, the remaining 40% (242/606) experienced MRD conversion with a 5.7 y median time from ASCT and 6.3 y from diagnosis. The risk of clinical relapse was significantly elevated in patients with MRD conversion compared to sustained MRD negativity (73%, 177/242 vs. 5%, 18/364; R.R. = 3.5; P&lt; 0.0001). The median level of MRD positivity (&gt; 0.2 ratio of MM cells to normal plasma cells) also highly correlated with relapse ( P&lt; 0.0001). Loss of MRD negativity preceded clinical relapse by a median time of 1.1 years. Loss of MRD negativity without clinical relapse was seen in 27% (65/242). MRD conversion was associated with an inferior PFS and OS (PFS: 10.2 y vs. NR; P &lt; 0.0001, H.R. 18.7; 95% CI 13.3 - 26.3 and OS: 26.1 y vs. NR; P= 0.01, H.R. 1.7; 95% CI 1.1 - 2.6). Furthermore, when MRD conversion was within 5 y of diagnosis compared &gt; 5 y, patients had a worse OS ( P &lt; 0.0001, H.R. 17.2; 95% CI 7.8 – 37.8). We also observed that MRD conversion later than 5 years from diagnosis did not affect the OS. In a subset of patients (n = 144) the timing of first MRD negativity following treatment was available. Attainment of MRD negativity within 6 months of diagnosis compared to any time after 6 months was predictive of future MRD conversion (65%, 17/26 vs.42%, 49/118; P = 0.03) and clinical relapse (54%, 14/26 vs.28%, 33/118; P = 0.02). Conclusions: MRD conversion occurs in a significant proportion of MM patients (40%) on long-term follow-up and predicts future clinical relapse. Significance of MRD conversion has a temporal relationship from diagnosis and portray inferior clinical outcome particularly within 5 years of diagnosis.
Metabolism-based GP-2250 in combination with gemcitabine as a novel approach to pancreatic cancer: A mouse xenograft study.
Authors: Chris Braumann, Marie Buchholz, Britta Majchrzak - Stiller, Stephan Hahn, Waldemar Uhl, Anup Kasi, Dr. Thomas Mueller
Journal: Journal of Clinical Oncology (2020)

e16750 Background: GP-2250, a novel oxathiazine derivative, displayed apoptotic cytotoxicity against various tumor cell lines but not normal cells. It was therefore tested whether its antineoplastic potential - alone or in combination – could be leveraged specifically against pancreatic cancer. Methods: GP-2250 is a cancer metabolism-based therapeutic. It depleted metabolic energy through inhibition of the enzyme GAPDH (glyceraldehyde-3-phosphate dehydrogenase) which is rate limiting for aerobic glycolysis. ATP was decreased in a time- and dose-dependent manner in pancreatic tumor cell lines and ROS was increased. Mitochondrial dysfunction was triggered by an increased expression of Bax and decreased expression of Bcl2, leading to apoptosis. Cytotoxicity of GP-2250 was ROS-dependent. It was blocked by N-acetylcysteine. Results: GP-2250 substantially increased the sensitivity of pancreatic tumor cells to various chemotherapeutics in particular to gemcitabine (Gem). At doses which were inactive or barely active per se, the combination of GP-2250 and Gem caused striking cytotoxicity in patient-derived primary tumor cells in vitro, pointing to a strong synergy between the two agents. This finding was substantiated in vivo by patient-derived xenograft (PDX) studies in nude mice. While GP-2250 and Gem, given as monotherapy (500 mg/kg and 50 mg/kg respectively, 2x/week), showed only a limited antineoplastic response, the combination treatment resulted in a significantly higher anti-tumor activity as shown in further PDX. Tumor regression was found in 5 out of 9 PDX based on RECIST criteria. Stable disease was reached in 3 of the remaining grafts. In 1 xenograft, which was unresponsive to Gem, the combination treatment nevertheless achieved a reduction in tumor growth which significantly exceeded that of GP-2250 monotherapy. Conclusions: GP-2250 is a novel cancer metabolism-based therapeutic. GP-2250, in combination with Gem, strongly reduces tumor growth in patient-derived xenografts exceeding by far the response to monotherapy. GP-2250 is being evaluated in a Phase I clinical trial in patients diagnosed with advanced pancreatic cancer (Clinical Trial NCT03854110).