tbuckley/cabot-search huggingface dataset:
Sarcopenia and clinical evaluation in predicting treatment tolerability and outcomes in aggressive non-Hodgkin B cell lymphoma.
Authors: Samuel Bernard Drory, Marie-France Forget, Han Ting Wang, Isabelle Fleury, Imran Ahmad, Laurence Marchand
Journal: Journal of Clinical Oncology (2020)

e24018 Background: Sarcopenia is associated with decreased treatment tolerance and overall survival in aggressive large B-cell lymphoma, the most common non-Hodgkin lymphoma (NHL) in the geriatric population. The impact of sarcopenia on event-free survival (EFS) in older adults with an aggressive B-cell NHL remains unclear. Our primary endpoint was to evaluate the association between sarcopenia and 6-month EFS in adults aged 65 and older diagnosed with an aggressive B-cell NHL. Methods: We performed a retrospective cohort study of adults 65 years or older diagnosed with an aggressive B-cell NHL between July 1 st 2014 and June 30 th 2018 who completed 1st line chemotherapy in an academic center. Sarcopenia was defined as the lowest tertile of psoas muscle index (PMI). Psoas muscle area was measured on a single axial slice at L4 using CoreSlicer software, and divided by height squared. EFS defined as no death, relapse or hospitalisation, was compared between sarcopenic and non-sarcopenic individuals using Kaplan-Meier curves and multivariable Cox regression. Results: In our cohort of 62 older adults, median age was 74 (interquartile range (IQR): 69-78) and median PMI was 7.2 cm 2 /m 2 (IQR: 5.9-8.4). Twenty patients were sarcopenic with a median PMI of 5.5 (4.8-6.3) cm 2 /m 2 . Most patients (56%) received full dose chemotherapy. Among patients who received an attenuated dose of chemotherapy, the percentage of patients with sarcopenia was similar to the one of patients receiving full dose chemotherapy (39% vs 24%, p=0.200). After controlling for age, sex, ECOG, cardiac disease, creatinine, LDH and hemoglobin levels, sarcopenia was associated with a lower EFS (HR 3.5, 95%CI: 1.1-11, p=0.032). Although sarcopenia was not associated with the choice of an attenuated chemotherapy intensity, when stratifying for chemotherapy intensity, there was a trend in favor of decreased EFS with sarcopenia in the full dose group (p=0.095), which did not reach statistical significance. Conclusions: Sarcopenia is associated with a lower 6-month EFS in older adults who completed first line chemotherapy. These individuals may benefit from pre-chemotherapy geriatric evaluation and tighter follow-up.
Rituximab in treatment of hematological system disorders
Authors: Xiangyun Dai, Tao Wu, Dongfeng Mao
Journal: BMJ (2018)

Rituximab is a human/mouse chimeric monoclonal antibody against CD20 antigen of B cells. It is one of the earliest monoclonal antibodies successfully used in the treatment of malignant tumors. In recent years, a number of studies have shown that rituximab can induce apoptosis of CD20-expressing B lymphocytes through antibody-dependent cytotoxicity, complement-dependent cytotoxicity and direct apoptosis induction. Combined with chemotherapy, rituximab can significantly enhance the therapeutic effect on aggressive lymphoma. In addition, rituximab is also play an increasingly important role in the treatment of primary immune thrombocytopenia, autoimmune hemolytic anemia and other autoimmune diseases, neuromyelitis optica, and lymphocytic proliferative diseases after stem cell transplantation.


Key words: 
Hematologic diseases; Lymphoma; Hematopoietic stem cell transplantation; Rituximab
Associations between patient-reported outcomes and physiatry assessments in an integrative model of a survivorship clinic.
Authors: Hira Latif, Kristi D Graves, Cristina Kline-Quiroz, Patrick Martone, Asma Ali Dilawari
Journal: Journal of Clinical Oncology (2020)

e14032 Background: The Institute of Medicine and Commission on Cancer recommends delivery of comprehensive survivorship care to all cancer survivors. While models exist for high-quality survivorship care, institutions encounter barriers such as lack of resources and training in cancer survivorship. We introduce a shared-care model with physical medicine and rehab (PM&amp;R) to provide comprehensive care to cancer survivors at MedStar Washington Hospital Center. Methods: We implemented a bimonthly survivorship clinic in September 2018, staffed by a medical oncologist, oncology fellow and a cancer rehabilitation fellow. We assessed patient reported outcomes through PROMIS short forms for physical functioning, companionship, satisfaction with social roles and depression. Physiatry assessments included the 6-minute walk test and the Timed Up and Go test. All patients received a treatment summary and survivorship care plan. Results: We evaluated 30 cancer survivors between Sept 2018 and December 2019; mean age was 55.6 years (SD = 10.6 years). Majority were female (60%) and Black (60%). Most patients were overweight or obese (93%) with a mean body mass index of 30.6 mg/m 2 (SD = 4.7). Breast (43%) and hematologic malignancy (33%) were the most common cancer diagnoses. The median time between cancer remission and the clinic visit was 16 months (Range = 1 to 65 months). The average score for Timed Up and Go test was within the reference normal value of &lt; 12 sec (8.22 seconds, n = 23). Average distance for the 6-minute walk test was 465.87 meters (n = 18). Survivor age was negatively correlated with the distance walked for the 6-min walk test (r = -0.51, p = 0.027). Better psychosocial functioning assessed with PROMIS were significantly associated with lower scores on the Timed Up and Go Test: satisfaction with social roles (r = -0.67, p = 0.033) and companionship (r = -0.64, p = 0.046); we identified a trend between Timed Up and Go scores and depression (r = 0.47, p = 0.099). Conclusions: An integrative survivorship clinic to provide multidisciplinary survivorship care is a feasible model and results suggest that patients’ physical functioning is significantly associated with psychosocial outcomes. Our approach highlights the importance of assessing both physical functioning and patient-reported outcomes. Future research can evaluate assessments of these outcomes over time.
A nomogram based on genetic and clinicopathologic features to predict the nonsentinel lymph node metastases in Chinese women breast cancer patients.
Authors: Liling Zhu, Ke Liu, Fengyun Li, Wentao Liang, Wenzhao Shi, Gang Feng, Jiandong Wang
Journal: Journal of Clinical Oncology (2020)

e12577 Background: Sentinel lymph node biopsy (SLNB) is the standard treatment for breast cancer patients with clinically negative axilla. However, axillary lymph node dissection (ALND) is still the standard care for sentinel lymph node (SLN) positive patients. Clinical data reveals 20–60 % of patients without non-sentinel lymph node metastasis (NSLNM) after ALND. Unnecessary ALND increases the risk of lymphedema and detracts from quality of life. In this study, we expect to develop a nomogram based on genetic and clinicopathologic features to predict the risk of NSLN metastasis in SLN-positive Chinese women breast cancer patients. Methods: This retrospective study collected data from 310 women breast cancer patients who underwent SLNB followed by ALND and without any neo-adjuvant therapy in Chinese PLA General Hospital, China, between 2016 and 2017. Genetic features contain 96 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility and prognosis based on the GWAS studies and clinical information. SNP genotyping was identified by the quantitative PCR detection platform. The genetic features were divided into two clusters by the gene functions and signaling pathways. The polygenic risk score (PRS) was used to evaluate the combined effect of each SNP cluster. Least absolute shrinkage and selection operator (LASSO) regression model was adopted for feature selection and nomogram construction. Internal validation was performed and the area under ROC curve (AUC) was assessed. Results: 81 patients of 310 patients (26%) had a positive axillary NSLNM. The LASSO regression analysis identified the clinicopathologic characteristics including molecular subtype, cN-stage, number of positive SLNs and number of negative SLNs as significant predictors of NSLNM. Furthermore, two SNP clusters were also showed statistically significant in the prediction of NSLNM. In internal validation, the average AUC of the nomogram was 0.795 and the model was well calibrated. Conclusions: We present a new nomogram by combining genetic and clinicopathologic factors to achieve higher sensitivity and specificity comparing with traditional clinicopathologic factors to predict NSLNM in Chinese women breast cancer. It is recommended that more validations are required in prospective studies among different patient populations.
AGEN1181, a clinical stage Fc-engineered anti-CTLA-4 antibody with improved therapeutic potential for the treatment of patients with advanced malignancies.
Authors: Steven O'Day, Chethan Ramamurthy, Andrea J. Bullock, Anthony B. El-Khoueiry, Lernik Ohanjanian, Anna Wijatyk, Waldo Ignacio Ortuzar Feliu, Irina Shapiro, Marek Ancukiewicz, Dhan Chand, Jennifer Buell, Michael S. Gordon
Journal: Journal of Clinical Oncology (2020)

TPS3157 Background: AGEN1181 is a novel Fc-optimized anti-CTLA4 antibody, currently being evaluated in an ongoing multi-center, open-label, phase 1 study in all advanced solid tumors as mono-therapy and combination with anti-PD-1 antibody, AGEN2034 (NCT03860272). AGEN1181 is Fc-engineered to harness a novel mechanism for enhanced FcγR-dependent functionality relative to first-generation CTLA-4 antibodies. In pre-clinical models, AGEN1181 enhances T cell priming, depletion of intratumoral regulatory T cells (Treg) and improved memory formation compared to first-generation anti-CTLA-4 antibodies. Most notably, AGEN1181 demonstrates improved binding to FcyRIIIA and superior T cell responsiveness in populations that only express the low affinity FcγRIIIA receptor relative to first-generation IgG1 CTLA-4 antibodies. The combination of AGEN1181 and AGEN2034 further enhances T cell activation and effector function. Methods: This phase 1 study is an open-label, multi-center dose-escalation designed to evaluate the safety, tolerability, dose limiting toxicity (DLT) PK, and pharmacodynamic profiles of patients with refractory advanced solid tumors who did not receive an anti-CTLA4 previously. The study is being conducted in 3 arms; with patients assigned using a standard 3+3 dose escalation design in the mono-therapy arms with AGEN1181 and an accelerated design in the combination with AGEN2034 arm. AGEN1181 is administered as IV infusion as mono-therapy on Day 1 of every 3 weeks (0.1,0.3,1,2,4 mg/kg), every 6-weeks (1,2,4 mg/kg) in parallel cohorts and every 6-weeks (0.1,0.3,1,2,4 mg/kg) in combination with AGEN2034 (3mg/kg Q2Weeks) until disease progression or unacceptable toxicity (maximum 2 years). All 3 Arms are open and enrolling patients. The study is expected to enroll approximately 80 evaluable patients with solid tumors. Dose reductions are not allowed in the event of AGEN1181-related toxicities. Currently 3 cohorts have been completed, first cohort in the combination arm and the fourth cohort in the monotherapy arm are enrolling. Preclinical and clinical assessment of AGEN1181 supports continued development as a potential therapy for refractory or relapsed advanced solid tumors. Clinical trial information: NCT03860272 .
Trends in management of locally advanced large cell neuroendocrine carcinoma of the lung.
Authors: Vladimir Limonnik, Stephen Abel, Athanasios Colonias, Dulabh K. Monga, Gene Grant Finley, Rodney E. Wegner
Journal: Journal of Clinical Oncology (2020)

e21073 Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare pulmonary malignancy with clinicopathologic features of both non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The optimal treatment approach for LCNEC is not well established, likely a result of the histology’s underrepresentation in randomized clinical trials. Given the paucity of available data regarding LCNEC management, we queried the National Cancer Database (NCDB) to describe trends in management, identify predictors of treatment receipt, and compare outcomes in patients receiving chemotherapy (ChT) and chemoradiotherapy (CRT). Methods: We identified patients with locally advanced (Stage III) LCNEC of the lung treated with definitive ChT or CRT between the years of 2004-2015. Odds ratios were calculated to determine predictors of CRT receipt. Multivariable cox regression was used to determine predictors of overall survival. Results: Using the above criteria, 6,802 patients were identified, 46% of whom received CRT (n = 3,153) while 39% (n = 2,644) received ChT alone. Median age of the entire cohort was 68 years old. Most patients had T4 (35%) and N2 (59%) disease. Median overall survival was 11.9 months (11.3-12.6) in patients receiving ChT compared to 16.1 months (15.4-16.9) in patients receiving CRT (p &lt; 0.0001). Overall survival at 1, 3, and 5 years was 50%, 20%, and 13% versus 60%, 27%, and 18%, in patients receiving ChT and CRT, respectively. Older patients and those with higher comorbidity scores were less likely to receive CRT; whereas patients with higher education level, treatment receipt at an academic/research program facility, N2 disease, and later treatment year were more likely to receive CRT. On multivariable analysis, older age, greater comorbidity score, presence of N2 disease, and presence of T4 disease were all associated with decreased OS, whereby female sex, private insurance, higher income, lower T stage, and more recent treatment were associated with increased overall survival. CRT receipt was an independent predictor of increased overall survival. Conclusions: Definitive CRT was an independent predictor of increased overall survival in patients with locally advanced LCNEC of the lung. Findings from our study may help guide potential areas of future investigation to help define an ideal treatment approach for LCNEC.
A survey on chronic heart failure management in community physicians in Chengdu
Authors: Xiu-qiong Yu, Hui Jiang, Mei Dai, Jiong Tang
Journal: BMJ (2013)

A questionnaire survey on chronic heart failure management was conducted in 110 physicians from Xindu, Supo, Jiajiang and Xinhua community hospital in Chengdu from January 2007 to June 2010. Results showed that 77.3% (85/110) of community physicians lacked knowledge about prevention, diagnosis and treatment of chronic heart failure, and the diagnostic accuracy rate was only 51.3% (40/78) in these community hospitals. There was lack of awareness of the guideline of chronic heart failure: the rate of β blockers use was 15.0% (6/40) and only 5.0% (2/40) used the target dose; the rate of angiotensin converting enzyme inhibitor use was 17.5% (7/40) and only 7.50% (3/40) used the target dose. In addition, 90% (99/110) of community doctors lacked the education and management for patients with heart failure. The survey suggests that the current situation of chronic heart failure management in community physicians in Chengdu is unsatisfactory. It is necessary to strengthen the training of community physicians.


Key words: 
Heart failure; Community health services
KarMMa-RW: A study of real-world treatment patterns in heavily pretreated patients with relapsed and refractory multiple myeloma (RRMM) and comparison of outcomes to KarMMa.
Authors: Sundar Jagannath, Yi Lin, Hartmut Goldschmidt, Donna Ellen Reece, Ajay K. Nooka, Paula Rodríguez Otero, Kosei Matsue, Nina Shah, Larry D. Anderson, Jr, Kimberly Wilson, Arlene S. Swern, Faiza Zafar, Amit Balkrishna Agarwal, David Samuel DiCapua Siegel
Journal: Journal of Clinical Oncology (2020)

8525 Background: RRMM patients (pts) triple-class exposed (to immunomodulatory drugs [IMiDs], proteasome inhibitors [PIs] and anti-CD38 monoclonal antibodies [mAbs]) have limited treatment (tx) options. The ongoing phase II KarMMa study (NCT03361748) is examining idecabtagene vicleucel (ide-cel; bb2121), a BCMA targeted CAR T cell therapy, in RRMM pts with ≥3 prior regimens (IMiD, PI and CD38 mAb inclusive) who are refractory to their last tx per IMWG criteria. This study aimed to 1) assess tx patterns and outcomes in real world (RW) RRMM pts similar to the KarMMa population and; 2) compare outcomes with SoC in a synthetic cohort vs ide-cel in KarMMa. Methods: In this global, noninterventional, retrospective study (KarMMa-RW), pt-level data from clinical sites, registries and databases were collated into a single data model. RW pts meeting KarMMa eligibility criteria (eligible cohort; EC) were compared with KarMMa (N = 128) using trimmed stabilized inverse probability of tx weighted propensity scores (IPTW PS) for pts in both studies with Poisson regression for ORR and ≥VGPR, and Cox models with study as a term for PFS. All models were adjusted for unbalanced covariates. Results: Of 1949 RW pts, 1171 were refractory to last regimen (median age, 68 y; median no. of prior regimens, 5; triple-class refractory, 41%). Further selection for subsequent tx, organ function and no comorbidities yielded 190 EC pts who had &gt; 90 distinct tx regimens. With a median follow-up of 11.3 mo (KarMMa) and 10.2 mo (EC) at data cutoff (Oct 30, 2019), ORR, ≥VGPR and PFS were significantly improved in KarMMa vs EC (Table). Conclusions: Results from the KarMMa-RW study confirm that there is no clear SoC for heavily pretreated RW RRMM pts and responses are suboptimal with currently available therapies. Ide-cel showed deep, durable responses and significantly improved PFS in RRMM pts, representing a potential new tx option in RRMM. Clinical trial information: tbd . [Table: see text]
Development and validation of targeted treatments for the rare tumor syndrome infantile myofibromatosis.
Authors: Ying Chen, Srirupa Das, Deep Pandya, Jean-Noel Billaud, Anna Reva, Annabel Roth, Peter Remsen Dottino, Hakon Hakonarson, John Martignetti
Journal: Journal of Clinical Oncology (2020)

e22519 Background: Infantile myofibromatosis (IMF; MIM 228550) is an autosomal dominant disorder characterized by fibroblastic tumors of skin, muscles, viscera and bones. Tumor growth may begin during fetal development, where it may lead to early death, and/or can be present throughout adult life. We originally demonstrated that mutations in the platelet-derived growth factor receptor beta gene (PDGFRb) result in IMF. Currently, beyond surgical removal and chemotherapy, there is no effective treatment. Using an integrated genomic, bioinformatic and functional approach based on analysis of patient-derived IMF cells and mouse models, encapsulating multiple IMF-causing PDGFRb mutations, we sought to identify potentially druggable targets and validate them in preclinical models. Methods: Patient samples were genetically characterized by whole exome (WES) and RNA sequencing. Patient-derived cell lines from tumor and adjacent normal tissue (PDCL) were generated from a patient with a novel F864L mutation. This IMF-causing mutation along with two others, R561C and P660T, were stably expressed in BAF3 cells for functional characterization. PDCL-F864L were used to generate an orthotopic mouse IMF model. Results: WES of paired patient tumor, PDCL and germline samples confirmed a novel germline PDGFRb mutation (c.2590T &gt; C, Phe864Leu). Using PDCL, the F864L mutation was shown to result in constitutive PDGFRb activation. Based on these findings, the tyrosine kinase inhibitors Imatinib and Sunitinib were chosen as candidate therapies. As predicted, they markedly inhibited cell proliferation and blocked PDGFRb activation and downstream signaling molecules AKT and ERK. Similar results were obtained in F864L, R561C and P660T mutant expressing BAF3 (natively PDGFRb null) cells when compared to WT PDGFRb expressing controls. Having established these findings using cultured cells, the effects of Imatinib and Sunitinib were next tested on an orthotopic mouse model. Given to IMF tumor mice as a single drug, both drugs markedly and sustainably decreased tumor size compared to control mice. Conclusions: Our findings demonstrate that IMF-associated PDGFRb mutations are gain-of-function mutations. Using patient-derived IMF models, Imatinib and Sunitinib effectively target these GOF mutations through PDGFRb signaling pathway inhibition. These findings provide preclinical data for targeted treatment of this rare cancer.
Blue-green light phototherapy for preterm jaundice
Authors: Ying Liu, Yu-xin Zhou
Journal: BMJ (2011)

Objective To evaluate the efficacy of blue-green light phototherapy for jaundice in preterm newborns.Methods Total 124 preterm newborns with birth-weight below 2000 g were included in this study.Infants in group A (gestation age ≤32 weeks or/and instability,n =72) were treated with bluegreen light (group A1 ) or with single side blue light (group A2) randomly.Infants with gestation age ＞32weeks or/and stability (n =52) were also treated with blue-green light (group B1 ) or with single side blue light ( group B2) randomly.Peak levels of serum bilirubin ( PSB),the withdrawal time of jaundice and the duration of phototherapy were compared between groups.Results Group A:PSB of groupAl was lower than that of groupA2 [ (219 ± 31 ) μmol/L vs.( 257 ± 39 ) μ mol/L,P ＜ 0.01 ].The withdrawal time of jaundice group Al was earlier than that of group A2 [ ( 10.3 ±3.0) d vs.( 16.2 ±4.2) d,P ＜0.01 ].The duration of phototherapy of groupA1 was shorter than that of group A2 [ (87 ±34) h vs.(23 ±49) h,P ＜0.01 ].Group B:There were no differences in PSB and withdrawal time of jaundice between two subgroups ( P ＞0.05).The duration of phototherapy of groupB1 was shorter than that of group B2 [ (59 ±23) h vs.(73 ±74) h,P ＜ 0.05 ].Conclusion Blue-green light phototherapy is more effective than single side of blue light in treatment of jaundice in preterm newborns.

Key words: 
Jaundice,neonatal;  Phototherapy ;  Treatment outcome
乙型肝炎的抗病毒治疗
Authors: 陈宝敏
Journal: BMJ (2006)

慢性乙型肝炎(乙肝)是世界上第10大致死疾病,有超过3.5亿的人口感染,每年大约有120万人死于乙肝相关的慢性肝病.我国为慢性乙肝高发区,目前全国约有1.3亿乙型肝炎病毒(HBV)携带者,慢性肝炎患者约有1 300万.HBV感染可以导致终生感染、肝硬化、肝癌、肝衰竭,以致死亡.慢性乙肝治疗的关键是抗HBV治疗.近10年,对乙肝抗病毒治疗的研究取得了相当多的进展。