tbuckley/cabot-search huggingface dataset:
Evaluation of the differences between extramedullary and bone marrow relapse in adult acute lymphoblastic leukemia patients in terms of clinical features and survival outcomes.
Authors: Nilgun Sayınalp, Rafiye Ciftciler, Yahya Buyukasik, IC Haznedaroglu, Salih Aksu, Haluk Demiroglu, Hakan Goker, Osman Ozcebe
Journal: Journal of Clinical Oncology (2020)

e19516 Background: Acute lymphoblastic leukemia (ALL) in adult patients is an uncommon and difficult-to-treat hematological malignancy that is characterized by excess lymphoblasts in the bone marrow (BM). Although many patients achieve remission with chemotherapy, relapse rates are high and survival outcomes in adults are worse than pediatric patients. With uncontrolled proliferation and accumulation of these lymphoblasts, normal hematopoiesis is suppressed and infiltrates various extramedullary (EM) regions. The aim of this study is to evaluate the difference between EM and BM relapse in adult ALL patients in terms of clinical features and survival outcomes. Methods: In this study, we retrospectively analyzed 108 patients who were diagnosed as ALL and treated in our tertiary care center between 2003 and 2019. Statistical analyses were performed using the SPSS software version 25. Results: The study included 108 patients, consisting of 64 males and 44 females with a median age of 30 (range: 17-79 years). The majority of cases were B-cell in origin; 87 (80.6%) patients had B-ALL and 21 (19.4%) had T-ALL. Median follow-up duration for all patients was 21.1 months (range: 0.49-158.7 months). In the follow-up, 28 patients (25.9%) were received allogeneic hematopoietic stem cell transplantation. A total of 27 (25%) patients relapsed during the follow-up period. In 15 (13.9%) of 27 patients, only BM relapse was observed. EM relapse was observed in 12 (11.1%) patients. EM localizations were identified: brain [n = 2, 1.8%], lung [n = 1, 0.92%], retroperitoneum region [n = 1, 0.92%], kidney [n = 2, 1.8%], breast [n = 1, 0.92%], vertebral column [n = 3, 2.7%], spleen [n = 1, 0.92%], and uvea [n = 1, 0.92%]. All of the patients relapsed with bone marrow were B-ALL. Five of the patients (41.7%) with EM relapse were T-ALL (p = 0.006). No significant difference was observed in terms of gender (p = 0.16) and age (p = 0.12) in patients with BM relapse and EM relapse. Median overall survival (OS) was 42.3 months (95% CI: 15.6-69.0) for patients with BM relapse and 32.8 months (95% CI: 20.0-45.5) for patients with EM relapse (p = 0.42). Conclusions: In conclusion, EM relapse is common in ALL patients. We observed that EM relapse is more frequent, especially in patients with T-ALL cell origin. no significant difference was observed in both groups in terms of OS. ALL patients should be carefully followed up in terms of EM relapses as well as bone marrow relapse.
Association of rs28714259 polymorphism with a risk of early-onset chronic anthracycline-mediated cardiotoxicity in patients with breast cancer.
Authors: Dmitry Yu. Gvaldin, Natalya N. Timoshkina, Ekaterina P. Omelchuk, Larisa N. Vashchenko, Anastasia S. Ratieva, Liubov Yu Vladimirova, Oleg I. Kit, Aleksandr E. Lisutin
Journal: Journal of Clinical Oncology (2020)

e13504 Background: Numerous pharmacogenetic studies have led to the identification of genetic polymorphisms associated not only with the development of cardiovascular disease, but also increase the risk of complications due to the use of anthracycline drugs, widely used in the treatment of cancer. The purpose of this study was to assess the prevalence of rs28714259 polymorphism and to study possible correlation with anthracycline-mediated cardiotoxicity (AMC). Methods: The study included 173 Caucasian patients (median age 55 years) with a diagnosis of breast cancer without diagnosed cardiovascular pathology who underwent treatment in the RRIO, Rostov-on-Don in 2019. For genotyping of SNP rs28714259, DNA was extracted from blood using DNA-sorb-B (AmpliSens, Russia) and HRM-PCR was performed on a CFX96 amplifier (Bio-Rad, USA). The presence of polymorphism was confirmed by Sanger sequencing with a Genetic Analyzer 3500 (ABI, USA). The obtained results were compared with European population (1000 Genome). Results: 13 patients (7.5%) with an early-onset of chronic AMC were founded after three courses of chemotherapy. The allelic frequency rs28714259 was 0.079, the frequency of AG genotypes was 0.135, and AA was 0.012. It was shown that the presence of this SNP leads to an increase risk of cardiovascular pathology at an early stage by more than 4 times (OR = 4.186, p = 0.006). In addition, when comparing with the European population, the highest probability of developing early-onset chronic AMC was determined for patients with the AA genotype (more than 22 times, p = 0.001). Conclusions: In this study, a statistically significant association of rs28714259 presence with developing early-onset chronic AMC was revealed, which seems promising for the early determination of the risk group in the management of cancer patients.
Analysis of risk factors for stroke-associated pneumonia
Authors: Jie Han, Jun-ping Wang, Ming Li
Journal: BMJ (2010)

Clinical data of 595 patients of stroke admitted to the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning were analyzed retrospectively, 310 (52. 1% ) of them with strokeassociated pneumonia (SAP). Early-onset pneumonia occurred in 225 patients (72.6%), and late-onset pneumonia in 85 (27.4%). Patients with length of hospital-stay equal to or more than two weeks accounted for (113 cases) 50. 3% of those with early-onset pneumonia, whereas patients with length of hospital-stay less than one week (60 cases) accounted for 70. 6% of those with late-onset pneumonia. Age above 65 years ( OR = 1. 037 ), diabetes ( OR = 1. 724), Glasgow coma scores equal to or less than eight ( OR = 0. 098 ),nasal feeding ( OR = 6. 640 ), administration of gastric mucosal protective drugs ( OR = 3. 581 ) and antibiotic prophylaxis ( OR = 2. 433) all were risk factors for SAP.

Key words: 
Cerebrovascular accident;  Pneumonia
Progress in diagnosis and treatment of Hashimoto′s thyroiditis
Authors: Lihong Gao, Xianghai Zhou
Journal: BMJ (2018)

Hashimoto′s thyroiditis is the most common autoimmune thyroid disease and also the primary cause of hypothyroidism. The disease is characterized by long course, slow development, complicated clinical presentation and coexistence with a variety of thyroid diseases. Misdiagnosis and missed diagnosis rates are high, therefore close attention should be attached clinically.


Key words: 
Hashimoto′s disease; Hyperthyroidism; Hypothyroidism
Advances of neural and psychological mechanism in visceral hypersensitivity of irritable bowel syndrome
Authors: 王静, 诸琦
Journal: BMJ (2008)

肠易激综合征(imitable bowel ayndrome,IBS)是一组以腹痛、腹泻、排便异常等症状为特征的肠道功能性疾病.其中腹痛被认为与患者增加的内脏敏感性密切相关.1973年,Ritchie[1]第一次报道IBS患者对结肠扩张性刺激的内脏敏感性高于正常对照组.随后越来越多的研究支持这一观点,即IBS患者具有内脏高敏感。
The association of tissue tumor mutational burden (tTMB) using the Foundation Medicine genomic platform with efficacy of pembrolizumab versus paclitaxel in patients (pts) with gastric cancer (GC) from KEYNOTE-061.
Authors: Kohei Shitara, Mustafa Özgüroğlu, Yung-Jue Bang, Maria Di Bartolomeo, Mario Mandalà, Min-hee Ryu, Caterina Vivaldi, Tomasz Olesinski, Hyun Cheol Chung, Kei Muro, Eric Van Cutsem, Julie Kobie, Razvan Cristescu, Deepti Aurora-Garg, Jia Lu, Chie-Schin Shih, David Adelberg, Z. Alexander Cao, David Fabrizio, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2020)

4537 Background: KEYNOTE-061 (NCT02370498) was a randomized, open-label, phase 3 study of pembrolizumab vs paclitaxel in pts with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with tumor progression after first-line therapy (N = 592). In this analysis, we evaluated tTMB using FoundationOne CDx (F1CDx; Foundation Medicine) in pts with gastric or GEJ cancer in KEYNOTE-061. Methods: In pts with evaluable F1CDx tTMB data (n = 204), we analyzed the association of tTMB with confirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) within each treatment arm using one-sided (pembrolizumab) and two-sided (paclitaxel) Wald test nominal P for logistic regression (ORR) and Cox proportional hazards regression (PFS; OS) adjusted for ECOG performance status; significance was prespecified at 0.05. The clinical utility of tTMB was assessed using the prespecified cutoff of 10 mut/Mb for F1CDx. Clinical data cutoff: Oct 26, 2017. Results: tTMB was positively associated with ORR ( P &lt; 0.001; AUROC, 0.68), PFS ( P &lt; 0.001), and OS ( P = 0.003) with pembrolizumab but not paclitaxel (ORR, P = 0.047; AUROC, 0.30; PFS, P = 0.605; OS, P = 0.084). Pt outcomes by tTMB cutoff are reported in the Table; prevalence of TMB ≥10 mut/Mb was 17%. In pts with microsatellite stable disease-only, HRs (95% CI) by treatment arm for OS by F1CDx cutoff were 0.40 (0.14-1.17) for tTMB ≥10 mut/Mb (n = 21) vs 0.97 (0.70-1.34) for tTMB &lt;10 mut/Mb (n = 168). Conclusions: In this exploratory analysis from KEYNOTE-061, tTMB as determined by F1CDx demonstrated a positive association with clinical outcomes with pembrolizumab, but not paclitaxel, in pts with GC; these findings are consistent with those reported with whole exome sequencing. Pembrolizumab demonstrated an OS benefit vs paclitaxel in the subgroup with tTMB ≥10 mut/Mb, which remained when pts with microsatellite instability-high disease were excluded. Clinical trial information: NCT02370498 . [Table: see text]
Racial and gender disparities in stage at diagnosis for bladder cancer: Results from the surveillance, epidemiology, and end results (SEER) program, 2007 to 2016.
Authors: Sachin Gupta, Monika Joshi, Xingran Weng, Li Wang
Journal: Journal of Clinical Oncology (2020)

e17032 Background: Little is known about the patterns of racial and gender disparities in bladder cancer (BC). This study will use national large database to explore those disparities. Methods: Data from the National Cancer Institute’sSurveillance, Epidemiology, and End Results (SEER) Program for cancer registries was used. Patients &gt; = 18 years diagnosed with BC in the years 2007-2016 were identified from SEER 18 database. We used the data year 2007 because that was the year when insurance status was first collected in SEER. Chi-square tests and multinomial logistic regression were used. Results: A total of 78,151 (females: 25.58%) patients were included, with 82.74% being non-Hispanic whites, 5.83% non-Hispanic blacks, 6.69 % Hispanics and 4.74% others. Distribution of stage 0 through stage IV at diagnosis was 51.97%, 23.21%, 12.11%, 4.10% and 8.61% respectively. Blacks (P &lt; 0.0001) and females (P &lt; 0.0001) were diagnosed at later stages as in Table. e.g., 14.54% of blacks were diagnosed at stage IV, compared to 7.97% of whites; and 11.03% of females at stage IV vs. 7.77% of males. Racial disparity exists for any given insurance status. Within every age group, gender disparity exists. For example, for those under 50 years of age, 12.81% of women vs. 8.16% of men were diagnosed at stage IV. After controlling for age, marital status and insurance type, both gender (P &lt; 0.0001) and race (P &lt; 0.0001) were statistically significant in predicting stage at diagnosis. Conclusions: Racial disparity in stage at BC diagnosis was strong, with blacks suffering most from the disparity. Females were more likely to be diagnosed at later stages, and this gender disparity exists in all age groups and was not due to women living longer. The existence of both racial and gender disparities in BC makes black women most vulnerable to late diagnosis than any other racial/gender group. Oncologists treating BC patients should be aware of the racial and gender disparity. More research needs to be done to help improve early access to health care amongst female and minority BC patients. [Table: see text]
Phase I study of radiotherapy (RT) & durvalumab in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) & follicular lymphoma (FL): The RADD study.
Authors: Eliza Anne Hawkes, Kate Manos, Geoffrey Chong, Jodie Palmer, Michael Patrick MacManus, Colm Keane, Andrew Mark Scott, Jake Shortt, David Ritchie, Leonid Churilov, Laura Johnston, Tom Witkowski, Allison Anne Barraclough, Sze Ting Lee, Wendi Lin, Rachel Koldej, Richard Khor
Journal: Journal of Clinical Oncology (2020)

TPS8075 Background: Most DLBCL &amp; FL responds well to first line treatment, yet relapsed disease outcomes are poor. PD1/PDL1 inhibitors yield high response rates in some lymphomas, but single agent therapy in heavily pre-treated pts are disappointing. RT stimulates anti-tumor immunity through several mechanisms and may enhance response to immune checkpoint inhibition (ICI). Concurrent ICI &amp; RT is synergistic in preclinical studies &amp; solid tumors, improving local &amp; distant (abscopal) response. RT to multiple disease sites may broaden the spectrum of tumor antigen release and overcome clonal variation between disease sites to further augment the immune response. Methods: RaDD (NCT03610061) is a phase I, 3+3 dose escalation study to determine the safety profile of escalating dose &amp; number of sites of RT in combination with Durvalumab (anti-PD-L1 antibody) in RR DLBCL &amp; FL. Eligible pts (i.e. ≥1 prior therapy, ineligible for auto-SCT, no contraindication to PDL1i) receive 5 fractions of external beam RT to target site(s). 5 RT dose &amp; site levels are included (dose range 2.5Gy-20Gy to 1-3 sites). Durvalumab 1500mg IV commences day 2 of RT and continues 4-weekly until confirmed disease progression. The DLT period is 28 days from start of RT. Primary endpoint is the recommended phase two dose (RP2D) of RT in combination with durvalumab. Secondary endpoints include response rates, PFS &amp; OS. Correlative studies will examine the tumour-immune system interaction; an exploratory PET substudy with novel tracers for durvalumab ( 89 Zr-Durvalumab) &amp; CD8+ T cells ( 89 Zr -Df-IAB22M2C) will also be performed. Projected enrollment for determination of maximum tolerated dose (MTD) &amp; RP2D is 6-30 pts pending toxicity. Recruitment will continue to 36 pts for secondary endpoint analysis. 9 pts are enrolled across cohorts 1-3 to date. Clinical trial information: NCT03610061 .
Is there a role for hypofractionated thoracic radiotherapy in limited-stage small cell lung cancer? a propensity score matched analysis.
Authors: Sondos Zayed, Hanbo Chen, Emma M Ali, George Rodrigues, Andrew Warner, David A. Palma, Alexander V Louie
Journal: Journal of Clinical Oncology (2020)

e21107 Background: Concurrent chemoradiotherapy is the standard of care for limited-stage small cell lung cancer (LS-SCLC). While conventional fractionation (CF) and hyperfractionation are the most commonly used radiotherapy schedules worldwide, hypofractionation (HF) continues to be a standard radiation regimen used in several countries. In the absence of randomized evidence comparing CF and HF, the aim of this study was to compare overall survival (OS), progression-free survival (PFS), and toxicity outcomes for CF and HF in LS-SCLC. Methods: In this single institution retrospective review, consecutive LS-SCLC patients treated between 2000-2013 with HF (40Gy/15, 45Gy/15, 45Gy/20 fractions) or CF (60Gy/30 or 66Gy/33 fractions) were included. Propensity scores were generated using a multivariable logistic regression model. Patients were matched on a 1:1 ratio with a caliper distance of 0.20. OS and PFS were estimated using the Kaplan-Meier method with differences evaluated using log-rank tests. As a sensitivity analysis, univariable and multivariable Cox regression was performed in all unmatched patients. Logistic regression was performed to identify predictors of all pulmonary and esophageal adverse events. Results: In the 117 patients, there were significant baseline differences between the CF and HF cohorts. Patients who received CF were older, smoked more often concurrently with treatment, had higher ECOG performance status, different T and N stage patterns, and more commonly received concurrent chemoradiotherapy and prophylactic cranial irradiation. After propensity score matching, 72 patients were included, 36 in the HF and CF cohorts respectively. No statistically significant difference was noted between matched HF and CF cohorts for OS (P = 0.724) or PFS (P = 0.862). Similarly, multivariable Cox regression revealed no differences in OS (P = 0.886) or PFS (P = 0.717) between HF and CF in all unmatched patients. There was no difference in any pulmonary (P = 0.350) or esophageal (P = 0.097) adverse events between matched HF and CF cohorts. Skin adverse events were significantly higher for CF (41.7%) compared with HF (16.7%, P = 0.020) in matched patients. No grade 5 adverse events were observed. Conclusions: In this propensity score matched comparison of HF and CF in LS-SCLC patients who underwent curative-intent radiation treatment, HF and CF were associated with comparable OS, PFS, and toxicity outcomes. HF may therefore be a reasonable alternative to CF, should its efficacy be confirmed in prospective studies.
Neural mechanisms of impaired executive function in untreated colorectal cancer patients.
Authors: David Anderson, Matthew Garlinghouse, Arica Hauger, Alison Moody, Ann M. Berger, Jean L. Grem
Journal: Journal of Clinical Oncology (2020)

e24170 Background: Cancer-related cognitive impairment (CRCI) affects 45% of colorectal cancer (CRC) patients prior to treatment. This study aimed to explore the neural mechanisms of CRCI in this severely understudied population by using a combination of neuropsychological and cognitive neurophysiology assessments. Methods: Newly diagnosed Stage I-IV CRC patients were recruited at a Midwestern tertiary medical center. Enrollment criteria included normal or corrected to normal vision and no prior cancer within 3 years. Healthy comparisons were recruited and demographically-matched to Stage III/IV patients scheduled to receive chemotherapy. Participants completed neuropsychological measures of processing speed, psychomotor speed, executive function, and verbal memory at study baseline. We recorded scalp electroencephalography while participants performed a computer-based cognitive task designed to measure control over spatial attention. Two event-related potentials were measured following presentation of a task-irrelevant spatial cue: (1) N2, a neural correlate of stimulus selection emerging approximately 160 milliseconds after stimulus presentation; and (2) N2pc, a neural correlate of spatial attention allocation emerging approximately 200 milliseconds after stimulus presentation. Results: CRC patients were enrolled within 4-8 weeks following surgery for Stage I (11%), II (31%), and III (35%) CRC; Stage IV patients (23%) started chemotherapy without surgery. Patients (n = 26) and controls (n = 14) were matched on age and gender; patients were trending toward lower education than controls (p = .06). Patients performed worse than controls on executive function assessments (Trials B: p = .049; Stroop: p = .025). N2 amplitudes were smaller in patients than controls (p = 0.032. N2pc amplitudes were larger in patients than controls (p = .092). N2 amplitudes were associated with Stroop interference scores (r = 0.50, p = .068). Conclusions: CRC patients demonstrated impaired executive function performance at baseline. Neurophysiological data suggest impairments may emerge from limited neural resources available for stimulus selection and poor control over spatial attention. Correlations between neurophysiological data and executive function performance suggest participants better able to overcome task-irrelevant interference had relatively more neural resources available for stimulus selection. Overall, these results suggest patients may be limited in their ability to focus their attention on caregiver and health care team instructions. Clinical trial information: NCT03683004 .
Efficacy of anti-programmed cell death-1/ligand 1 monotherapy for non-small cell lung cancer patients with active brain metastases.
Authors: Takehiro Tozuka, Satoru Kitazono, Hiroaki Sakamoto, Hiroshi Yoshida, Yoshiaki Amino, Shinya Uematsu, Takahiro Yoshizawa, Tsukasa Hasegawa, Ryo Ariyasu, Ken Uchibori, Noriko Yanagitani, Takeshi Horai, Makoto Nishio
Journal: Journal of Clinical Oncology (2020)

e14511 Background: The efficacy of anti-programmed cell death-1/ligand 1 (anti-PD-(L)1) for active brain metastases (BMs) is not established, because most clinical trials excluded patients (pts) with active BMs such as untreated, symptomatic, or unstable BMs. The aim of this study was to evaluate the efficacy of anti-PD-(L)1 monotherapy in non-small cell lung cancer (NSCLC) pts with active BMs. Methods: This retrospective study included NSCLC pts who had received anti-PD-(L)1 monotherapy in 2nd or later line between December 2015 and August 2019. Pts who had not evaluated BMs by CT/MRI before anti-PD-(L)1 were excluded. Pts were classified into those with or without active BMs which were defined as untreated or symptomatic BMs or BMs requiring systemic steroids. Progression free survival (PFS) and overall survival (OS) of pts with or without active BMs were compared. Intra-cranial and extra-cranial tumor responses were evaluated in pts with active BMs. Results: In this study, 242 pts who had received anti-PD-(L)1 monotherapy were identified and 197 pts were analyzed. Twenty-four pts were classified to pts with active BMs. Among pts without active BMs, 145 pts had no BMs and 28 pts had treated asymptomatic BMs. PFS of pts with active BMs was significantly shorter than that of pts without active BMs (1.3 versus 2.7 months; p &lt; 0.001). OS of pts with active BMs was significantly shorter than that of pts without active BMs (4.5 vs 16.3 months; p = 0.001). Intracranial response rate (RR) was 13.3% (2/15) and extracranial RR was 26.7% (4/15) in pts with active BMs. In multivariate Cox regression analysis, active BM, poor PS and EGFR/ALK(+) were selected as significant factors associated with poor PFS. Active BM and poor PS were selected as significant factors associated with poor OS. Conclusions: Anti-PD-(L)1 monotherapy is not recommend for pts with active BMs.
Cohort study on patients with metastatic colorectal cancer with integrated Chinese and western medicine.
Authors: Tong Zhang, Wenting He, Mo Tang, Yufei Yang
Journal: Journal of Clinical Oncology (2020)

e16030 Background: To investigate the efficacy of integrated Chinese and Western medicine in the treatment of mCRC in a cohort study (Registry No. ChiCTR-IOR-17010497). Methods: The survival outcome of patients receiving integrated Chinese and Western medicine was compared with that of patients receiving Western medicine alone. The study design was adopted with "continuous administration of traditional Chinese medicine for ≥ 3 months" as the exposure factor. Patients who met this exposure factor were assigned to the integrated Chinese and Western medicine cohort. Patients who did not meet this exposure factor were assigned to the Western medicine cohort. The overall survival, 5-year survival rate in the two cohorts were compared. Results: 335 subjects were assigned into two groups (Group A 129 patients, Group B 206 patients). The median overall survival (OS) in Group A and B were 19.2 months (95% CI 16.2–23.2) and 15.2 months (95% CI 13.3–17.2), P= 0.019. Group A demonstrated significantly longer OS and PFS than Group B in the following subgroups: female patients, right-side colon, first-line treatment, RAS mutation. Conclusions: Integrated traditional Chinese and Western medicine can prolong the survival of patients with mCRC. Clinical trial information: ChiCTR-IOR-17010497 .