tbuckley/cabot-search huggingface dataset:
Pre-transplant molecular minimal residual disease (MMRD) is associated with inferior outcomes in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation.
Authors: Muhammad Husnain, Krishna Komanduri, Jeremy Ramdial, Lazaros J. Lekakis, Trent Peng Wang, Mark Goodman, Denise L. Pereira, Amer Beitinjaneh, Douglas Carollo, Robert Ali, Yaqub Nadeem Mohammed, Junaid Arshad, Diana Byrnes, Eduardo Edelman Saul, Luis E. Aguirre, Antonio Martin Jimenez
Journal: Journal of Clinical Oncology (2020)

7547 Background: Allogeneic Stem Cell Transplant (alloSCT) continues to be the optimal consolidation strategy for many patients with AML; cytogenetic and molecular abnormalities are known predictors of post-transplant outcomes. There is increasing evidence that Molecular Minimal Residual Disease (MMRD) following induction has important prognostic implications and its value in the prediction of post-transplant relapse continues to be elucidated. We aim to evaluate the impact of genetics and pre-transplant MMRD on clinical outcomes following alloSCT. Methods: We retrospectively evaluated eighty-nine patients, ≥18 years with a diagnosis of AML in complete morphologic remission (i.e. &lt; 5% BM blasts by morphologic assessment) who received alloSCT between 01/2012-05/2018 at the University of Miami and for whom cytogenetic and comprehensive molecular data was available prior to transplantation. Patients were stratified into favorable, intermediate and poor-risk categories based on 2017 ELN criteria. MMRD was defined as persistent leukemia-specific mutations prior to transplantation (i.e. NPM1, FLT3, CEBPA, IDH1-2, RUNX1 and TP53). Persistence of DTA mutations (DNMT3A, TET2 and ASXL1) was not considered MMRD, patients with unavailable cytogenetic/molecular data at diagnosis were excluded. Results: Seventy-four (83%) patients were transplanted in CR1, myeloablative conditioning was used in 72% of patients. Two-year OS and LFS were 69.4% and 78.2%, respectively. Stratification by ELN criteria resulted in prognostic separation for patients transplanted in CR1: 2-year OS for favorable (87%), intermediate (68%) and adverse risk (51%) patients (p = 0.0417). The presence of MMRD was the strongest predictor of post-transplant outcomes for the whole cohort with 2-year OS and LFS of 29.4% and 37.1% (HR 5.45 [95%CI 2.43-12.3] p = 0.0001; HR 12.4 [95%CI: 3.76 to 39.8] p = 0.0001); respectively. Subgroup analysis confirmed that MMRD was associated with significantly inferior LFS for IM/favorable and adverse risk patients (HR: 6.76 [95% CI 1.12 to 40.9], p = 0.038). Conclusions: Pre-transplant MMRD was the most important prognostic factor for relapse and survival in our cohort of AML patients undergoing alloSCT. Correlation of MMRD with other transplant variables such as conditioning intensity, MRD status by MFC and the impact of pre-emptive/therapeutic strategies in high-risk patients continues to be explored.
Performance of the IBIS/Tyrer-Cuzick (TC) Model by race/ethnicity in the Women’s Health Initiative.
Authors: Allison W. Kurian, Elisha Hughes, Ryan Bernhisel, Braden Probst, Jerry Lanchbury, Susanne Wagner, Alexander Gutin, Jennifer Lee Caswell-Jin, Thomas E Rohan, Aladdin H. Shadyab, JoAnn E Manson, Dorothy Lane, Marcia L. Stefanick
Journal: Journal of Clinical Oncology (2020)

1503 Background: The TC model, a breast cancer (BC) risk assessment tool based on family cancer history, reproductive and lifestyle factors is used to guide BC screening and prevention. TC was developed and validated largely in non-Hispanic White (NHW) women. We evaluated the calibration and discrimination of TC version 7.02 among racially/ethnically diverse post-menopausal women enrolled in the Women’s Health Initiative (WHI) clinical trials or observational study. Methods: WHI enrolled post-menopausal women from 1993-1998 and followed them prospectively for BC incidence. We included women aged ≤80 years at enrollment with no prior BC or mastectomy and with data required for TC, including weight, height, ages at menarche, first birth and menopause, menopausal hormone therapy use and family history of breast or ovarian cancer in first or second-degree relatives. Calibration was assessed by the ratio of observed BC cases to the number expected by TC (O/E), with expected cases calculated as the sum of cumulative hazards. We tested for differential discrimination by race/ethnicity (NHW, African American, Hispanic, Asian/Pacific Islander, Native American, other) using Cox regression. Time to BC was modeled using age, race/ethnicity, TC estimate (transformed by log of relative lifetime risk), and a term for interaction between race/ethnicity and TC estimate. Results: During the follow-up period (median 18.9 years, maximum 23.4 years), 6,836 new BC cases were diagnosed among 91,893 women. TC was well-calibrated overall (O/E 0.95) in NHW and African Americans, but over-estimated risk for Hispanics (O/E 0.75, Table). Results suggested good calibration for Asian/Pacific Islanders and Native Americans, but sample sizes were small. Discrimination did not differ significantly by race/ethnicity (two-sided p-value for interaction = 0.33). Conclusions: TC provided similar risk discrimination among post-menopausal women of different racial/ethnic groups over nearly 20 years of follow-up; however, it overestimated risk for Hispanics. Future studies in diverse populations are warranted, with need for a more accurate breast cancer risk assessment tool for Hispanics. [Table: see text]
Survey on hospital beds utilization of rural and urban community health service centers in Shanghai
Authors: Yaling Li, Jie Gu, Shijie Fu, Xiaoyan Ou, Wei Chen
Journal: BMJ (2014)

Objective
To survey on utilization of hospital beds in rural and urban community health centers in Shanghai.


Methods
The hospital beds utilization was investigated in one rural and one urban community health service centers in Shanghai. The data of hospitalized patients in a selected day were surveyed with self-made questionnaire, including the demographic information of patients, the diseases category, the length of hospital stay, self-care ability of daily life (ADL score), the purpose of hospitalization, and the management after discharge.


Results
Patients aged over 60 y accounted for 100.0%(138/138)in urban center and 98.7%(76/77)in rural center. The three top disease categories were all cardio or cerebrovascular diseases in urban center accounting for 86.9%(120/138), while those in rural center were hypertension, cerebral infarction and acute/chronic bronchitis (or tumor) accounting for 65.0%(50/77). The mean length of hospital stay in urban and rural centers were 609.6 d and 253.8 d, respectively (F=2 604.00, P=0.000). Patients with severe dysfunction in urban and rural centers accounted for the 84.0%(116/138) and 32.5%(35/77), respectively(χ2=80.911, P=0.000) . Patients not willing to be discharged in urban and rural centers accounted for 87.7%(121/138)and 57.1%(44/77), respectively in city and rural centers(P<0.05).


Conclusions
The wards in community health centers mainly serve the elderly patients. There are differences in purpose of hospitalization, length of hospital stay, ADL scores of patients between rural and urban community health centers.


Key words: 
Community health service; Inpatients; Questionnaires
A randomized phase II/III trial comparing hepatectomy followed by mFOLFOX6 with hepatectomy alone for liver metastasis from colorectal cancer: JCOG0603 study.
Authors: Yukihide Kanemitsu, Yasuhiro Shimizu, Junki Mizusawa, Yoshitaka Inaba, Tetsuya Hamaguchi, Dai Shida, Masayuki Ohue, Koji Komori, Akio Shiomi, Manabu Shiozawa, Jun Watanabe, Takeshi Suto, Yusuke Kinugasa, Yasumasa Takii, Hiroyuki Bando, Takaya Kobatake, Tomoyuki Kato, Yasuhiro Shimada, Hiroshi Katayama, Haruhiko Fukuda
Journal: Journal of Clinical Oncology (2020)

4005 Background: The role of adjuvant chemotherapy after hepatectomy is controversial for liver only metastases from colorectal cancer (LM). Current recommendations for oxaliplatin-containing adjuvant regimen (FOLFOX) for LM are based on extrapolation of the results of the EORTC intergroup trial 40983, which showed that perioperative FOLFOX confirmed a progression-free survival benefit but did not affect overall survival (OS) in LM patients. We conducted a randomized controlled trial to determine if adjuvant modified FOLFOX (mFOLFOX) is superior to hepatectomy alone for LM. Methods: Eligible patients aged 20-75 years who had histologically proven colorectal adenocarcinoma with an unlimited number of LM were randomly assigned (1:1) to receive either adjuvant mFOLFOX6 (oxaliplatin 85mg/m 2 , l-LV 200 mg/m 2 , 5-FU bolus 400 mg/m 2 and 2400mg/m 2 over 48 h), for 12 cycles after surgery (CTX arm), or surgery alone (S alone arm). When treatment compliance after 9 courses of CTX was as high as expected in phase II, the registration was continued in phase III. The primary endpoint of phase III was disease-free survival (DFS), and the secondary endpoints were OS, toxicity, and sites of relapse. The planned sample size was 150 patients (pts) per arm, with a one-sided alpha of 5%, and 80% power detecting a 5y-DFS difference of 12% (25% with S alone vs. 37% with CTX). Results: Between Mar. 2007 and Jan. 2019, 300 patients were randomized. 151 pts were allocated to CTX, and 149 pts to S alone. When the third interim analysis of phase III was performed in Dec. 2019, the DSMC recommended the early termination of the trial because a statistically significant difference in terms of DFS but the futility in terms of OS was found. With a median follow-up period of 54 months for disease-free surviving patients, the 3y-DFS was 52.1% (95% CI 43.2 – 60.2) with CTX and 41.5% (33.2 – 49.6) with S alone (hazard ratio 0.63 [0.45 – 0.89], one-sided p = 0.002 &lt; 0.0163 for the one-sided alpha level at the interim analysis). However, the 3y-OS was 86.6% (79.2-91.4) with CTX and 92.2% (86.0 – 95.8) with S alone (hazard ratio 1.35 [0.84 – 2.19]). The 5y-OS was 69.5% (59.6-77.5) with CTX and 83.0% (74.5-88.9) with S alone. Median OS after recurrence was 38.4 months in the CTX arm and 87.6 in the S alone arm. Conclusions: DFS did not correlate with OS for LM. Postoperative chemotherapy with mFOLFOX6 improves DFS but worsens OS over surgery alone due to more deaths after recurrence in the CTX arm. Adjuvant mFOLFOX is not beneficial to patients after hepatectomy for LM. Clinical trial information: UMIN000000653 .
Boosted photocatalytic activity induced NAMPT-Regulating therapy based on elemental bismuth-humic acids heterojunction for inhibiting tumor proliferation/migration/inflammation
Authors: Yilin Song, Lifang Yang, Min Xu, Qianglan Lu, Wen Li, Chuchu Ren, Ping Liu, Yule Wang, Yan Zhu, Fengping Tan, Nan Li
Journal: Biomaterials (2020)
A sensitive and quantitative multimodal blood test for the detection of colorectal adenomas and cancer: Correlation with size and number of polyps.
Authors: Shai Friedland, Jennifer Y. Pan, Drew Watson, Yu Chen, Ashish Nimgaonkar, Zulfiqar Gulzar, Pratyush Gupta, Julian Lucas, Alex Atkins, Jr-Ming Lai, Ben Hsieh, Stephen Su, Austin Lim, Iris Ciu, Ploy Setthasap, John J. Sninsky, Rui Mei
Journal: Journal of Clinical Oncology (2020)

1555 Background: Colonoscopic polypectomy is the primary reason for declining colorectal cancer incidence and mortality. Epidemiological evidence has ordered the timing and risk of pre-cancerous adenomas, localized and invasive cancer along a 7-10 year continuum. The increased size and number of index polyps are correlated with an increased probability of progression to cancer and informs surveillance colonoscopies. Methods: A single-center, IRB-approved, prospective, blinded study was conducted at the VA Palo Alto Health Care System. Results for 354 patients with no prior diagnosis of CRC who were scheduled for colonoscopy are presented. Indications for colonoscopy were 86% asymptomatic and 14% with symptoms or positive-FIT. Patients had blood drawn immediately prior to colonoscopy. The test analyzes three biomarkers: circulating gastrointestinal epithelial cells (CEC), validated somatic mutations, and methylation (SEPTIN9) of cell-free DNA and uses incident risk to calculate a CMx Score, scaled from 0 to 100. Multivariate regression methods were used to assess the degree of association between the pre-defined CMx Scores and polyp sizes and number, adjusting for both DNA mutation and DNA methylation status. Results: There is a significant association between CMx Scores and polyp size (F value = 5.80, p-value = 0.017). DNA mutation (F value = 1.29, p-value = 0.263) and methylation status (F value = 0.34, p-value = 0.560) were non-significant. Similarly, there is a significant association between CMx Scores and number of polyps (F value = 23.71, p-value &lt; 0.0001). Again, DNA mutation (F value = 1.57, p-value = 0.210) and methylation status (F value = 1.34, p-value = 0.248) were non-significant. These results suggest that CMx Scores, which incorporate CEC, are providing predictive information of polyp sizes and number above and beyond DNA mutation and methylation status alone. Conclusions: A novel noninvasive multimodal blood-based assay that analyzes cell-free DNA for somatic mutations and methylation, CEC and integrates SEER incidence risk is significantly associated with polyp size and number. The opportunity to track progression and potentially inform colonoscopy interval is notable. [Table: see text]
Spatial analysis of tumor immune microenvironment (TIME) in patients treated with Bintrafusp alfa.
Authors: Houssein Abdul Sater, Jeffrey Robinson, Julius Strauss, Margaret Elena Gatti-Mays, Jason Redman, Charalampos S. Floudas, Jenn Marte, Lisa M. Cordes, Beatriz Walter Rodriguez, Andrew Wiseman, George Zaki, Fatima Karzai, Marijo Bilusic, Ravi Amrit Madan, Jeffrey Schlom, Arun Rajan, James L. Gulley
Journal: Journal of Clinical Oncology (2020)

3070 Background: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII receptor (TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. In preclinical models, bintrafusp alfa treatment promoted CD8+ T cell and NK cell activation, and both immune cell (IC) populations were required for optimal bintrafusp alfa mediated tumor control. However, the effect of bintrafusp alfa on TIME in humans has not been reported. Methods: In this unplanned interim analysis of a biomarker expansion cohort (NCT 02517398), patients (pts) with advanced non-small cell lung cancer (NSCLC) underwent paired biopsies (bx) before and on treatment with bintrafusp alfa (~ 50 days apart). The objective was to evaluate frequency and localization of tumor infiltrated ICs by IHC. Out of 12 pts, 7 had matched (Pre vs Post) tumor-containing specimens sufficient for multiplex immunofluorescence (MxIF) analysis of TIME. Four pts were excluded as Post bx histology for 3/12 [2 PR (partial response), 1 SD (stable disease)] was negative for tumor (necrosis or fibrosis) and 1/12 did not have a Post bx performed. Results: TIME study shows CD8 T cell infiltrates were increased in Post compared to Pre bx (median 161 vs 62/mm²; interquartile range [IQR] 65–396/mm² vs 31–135/mm²; p = 0·04). While M2 macrophages were also increased (median 800 vs 367/mm²; IQR 776–1131/mm² vs 171–831/mm²; p = 0·04), the ratio of M1/M2 was reversed in pts with SD (↑) compared to pts with PD (↓). Other ICs such as CD4, T-regs, NK cells and M1 macrophages were not changed. On average compared to baseline, M2 macrophages were &gt; 2 fold closer to every other IC in pts with PD, but &gt; 2 fold further from any IC in pts with SD. Tregs were relatively closer to other IC in PD pts. Linear Discriminant Analysis was also performed and results indicate that differential IC densities (mainly M1 macrophages and CD4 T cells) do perform as classifiers between long ( &gt; 5 months) and short ( &lt; 5 months) term responses. Conclusions: This study suggests that bintrafusp alfa not only can enhance intratumoral effector IC infiltrates (CD8) but also has a modulating effect on the spatial distribution of both M1/M2 macrophages within the NSCLC TIME. The differential proximity of M2 macrophages to other IC infiltrates and changes in M1/M2 ratios in association with response suggests that an M1/M2 macrophage balance is directly involved in response and/or resistance to bintrafusp alfa. Given the limited number of patients in this cohort, we intend to study effects of bintrafusp alfa in a larger cohort of patients. Clinical trial information: 02517398 .
Survey on sleep disorders in patients with Parkinson disease
Authors: Dongdong Wu, Wen Su, Shuhua Li, Jing He, Wei Du, Xinxin Ma, Huijing Liu, Kai Li
Journal: BMJ (2018)

Objective
To survey the prevalence and distribution of sleep disorders in patients with Parkinson disease (PD) and to analyze the influencing factors.


Methods
The prevalence and distribution of sleep disorders were surveyed with Parkinson Disease Sleep Scale (PDSS) among 206 PD patients. The association of sleep disorders with age, course of disease, cognitive function, motor function, depression, and the equivalent dose of levodopa (LED) was analyzed.


Results
The overall PDSS score in 206 patients was (116.9±21.4). The three most frequent items of sleep disorders were the overall sleep quality(181/206, 87.9%), difficulty in maintaining sleep(160/206, 77.7%)and nocturnal enuresis(151/206, 73.3%); the three least frequent items were early awaking(87/206, 42.2%), urinary incontinence(56/206, 27.2%)and hallucination(44/206, 21.4%). The three items with the lowest average scores were nocturnal enuresis(6.9±3.1), difficulty in maintaining of sleep(7.1±2.7)and overall sleep quality(7.1±2.0); three items with the highest average scores were audiovisual illusion(9.3±1.8), incontinence caused by motion disability(9.0±2.1) and early awaking with upper and lower limb pain(8.7±2.1). PD patients were divided into group 1 [Hoehn-Yahr(HY F=3.27, P=0.04) between group 1 and group 3. The linear regression analysis showed that the HAMD and the LED scores had the greatest influence on PDSS score (R2=0.142, 0.196).


Conclusion
PD patients have a variety of sleep symptoms. The treatment of large doses of dopamine and depression contribute to the occurrence of PD sleep disorders.


Key words: 
Parkinson disease; Sleep disorders; Depression; Questionnaires
Distribution of PD-L1 expression level across major tumor types.
Authors: Shun Xu, Minqi Tian, Xing Zhang, Chuang Qi, Chao Song
Journal: Journal of Clinical Oncology (2020)

e15176 Background: Programmed death-ligand (PD-L1) expression is an efficacy predictive biomarker in cancer immunotherapy. PD-1/PD-L1 axis can restore the host immunity against malignancies causing durable tumor remissions, and thus the level of PD-L1 protein expression is of critical clinical significance. However, the knowledge of PD-L1 expression level of patients with different malignancies is still inadequate understanding. Methods: Based on the percentage of positive tumor cells (TC value) identified by immunohistochemistry (IHC) method, the protein expression of PD-L1 was divided into three groups as g1 (TC &lt; 1%), g2 (1% ≤ TC &lt; 50%) and g3 (TC ≥ 50%). The expressions of PD-L1 from 1772 patients with malignancies across eight types including 133 patients with liver cancer, 35 patients with bile duct cancer, 94 patients with gastric cancer, 146 patients with colorectal cancer, 48 patients with pancreatic cancer, 76 patients with melanoma cancer, 33 patients with glioma and 1207 patients with lung cancer cases were made. The relationships between cancer types and PD-L1 expression were calculated via χ 2 test using SPSS v22.0. Results: The ratios of PD-L1 expression in three groups (g1, g2 and g3, respectively) across eight cancer types were 67.7, 30.8 and 1.5% in liver cancer, 65.7, 28.6 and 5.7% in bile duct cancer, 77.7, 20.2 and 2.1% in gastric cancer, 81.5, 18.5 and 0% in colorectal cancer, 64.6, 31.2 and 4.2% in pancreatic cancer, 50.5, 35.7 and 13.8% in melanoma, 30.3, 63.1 and 6.6% in glioma and 55.9, 34.0, 10.1% in lung cancer, respectively. Significant correlation between the PD-L1 expression and cancer types were found (χ 2 = 140.543, Cramer’s V coefficient = 0.199, p = 5.53×10 −23 ). The expression of PD-L1 in patients with lung cancer tended to be distributed in g3, in patients with melanoma tended to be distributed in g2, and in patients with gastric cancer, glioma, and colorectal cancer tended to be distributed in g1. Conclusions: Our study suggested the protein expression of PD-L1 was significantly heterogeneous among various cancer types and offered new references for cancer-specific characters of PD-L1 expression. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.
CC-486 is safe and well-tolerated as maintenance therapy in elderly patients (≥75 years) with acute myeloid leukemia (AML) in first remission following induction chemotherapy: Results from the phase III QUAZAR AML-001 trial.
Authors: Farhad Ravandi, Andrew Wei, Hartmut Dohner, Hervé Dombret, Gert J. Ossenkoppele, Michael Pfeilstöcker, Felicitas Thol, Georg Feldman, Maria Teresa Voso, Paula Marlton, Michael Harvey, Valeria Santini, Luana Fianchi, Anna Candoni, Ignazia La Torre, Barry Skikne, Keshava Kumar, Qian Dong, C. L. Beach, Gail J. Roboz
Journal: Journal of Clinical Oncology (2020)

7530 Background: About 40-50% of older patients (pts) with AML attain complete remission (CR) with induction chemotherapy (IC) but relapse is common.Effective, well-tolerated maintenance treatment (Tx) is needed for older pts in remission who are not eligible for hematopoietic stem cell transplant (HSCT). CC-486 is an oral hypomethylating agent that allows for extended dosing schedules ( &gt;7 days [d]/cycle) to sustain therapeutic activity. In the phase III placebo (PBO)-controlled QUAZAR AML-001 trial (NCT01757535), CC-486 maintenance therapy in pts with AML in first remission following IC produced significant improvements in overall and relapse-free survival. Here we report safety and tolerability findings among pt subgroups defined by age at study entry. Methods: Eligible pts were ≥ 55 yrs of age, with de novo or secondary AML, intermediate or poor risk cytogenetics, and ECOG PS ≤ 3; had achieved first CR or CRi after IC ± consolidation; and were not candidates for HSCT. Within 4 mo of CR/CRi, pts were randomized 1:1 to CC-486 300 mg or PBO QD on d 1–14 of repeated 28d Tx cycles. Safety was assessed across 3 age subgroups (≥ 55 to &lt; 65, ≥ 65 to &lt; 75, and ≥ 75 yrs) in pts who received ≥ 1 dose of study drug. Adverse events (AEs) were coded using MedDRA v. 22.0 and graded by NCI-CTCAE v. 4.0. Results: 469 pts ( &gt;99% of all enrolled pts) were evaluable for safety (CC-486 n = 236; PBO n = 233). Median age was 68 yrs (range 55-86). Age distribution was similar between the two Tx arms (Table). Between Tx arms, AE rates within each age stratum were similar to rates in the overall study population. The most common AEs (any grade) with CC-486 were GI events, which were more frequent than in the PBO arm across age groups. Within the CC-486 arm, AE rates were generally consistent across age groups, except for constipation, which was &gt; 20% more frequent in pts aged ≥ 75 yrs, and thrombocytopenia, which was ≥ 20% less frequent in this group (Table). Overall, 13% and 4% of pts in the CC-486 and PBO groups discontinued Tx due to AEs. Conclusions: In QUAZAR AML-001, CC-486 was generally well tolerated in all age groups, including elderly pts aged ≥ 75 yrs. Clinical trial information: NCT01757535 . [Table: see text]