tbuckley/cabot-search huggingface dataset:
Factors other than sheer numbers of blood cells in circulation may be responsible for clinical presentations in chronic myeloid leukaemia.
Authors: Nicolas Anthony Othieno-Abinya, Andrew Oluoch Odhiambo, Mohammed Shabbir Ezzi, Peter Omondi Oyiro
Journal: Journal of Clinical Oncology (2020)

e19527 Background: CML commonly presents with abdominal pain and swelling, and in up to about 50% of cases it is discovered incidentally due to abnormally elevated white blood cell (wbc) counts in circulation. Some present with bleeding tendency, others nusual presentations including hearing and visual loss whose pathogenesis is poorly understood also occur. Priapism presents rarely, attributed to hyperviscosity complicating wbc counts ≥ 250x10 9 /litre. Nonspecific symptoms also present. We wanted to interrogate the link between baseline myeloid elements in circulation, bone marrow blasts, and BCR-ABL values with clinical manifestations. Methods: Patients attending the Glivec International Patient Assistance Clinic at the Nairobi Hospital had records prospectively collected, and analyzed. These included demographic profiles, physical examination, and laboratory values. Absolute, range, median and mean counts for wbcs, absolute neutrophil counts (ANC), platelets, haemoglobin and BCR-ABL values, were tested against each of the clinical presentations. Results: There were 583 patients, males 322 (55.2%) and females 261 (44.8); mean age 39.8 years. Commonest symptom was abdominal swelling in 235 cases (40.3%); 70 (12%) experienced abdominal pain. Priapism occurred in 4 males (1.2%), blindness and deafness in 8 patients (1.4%). Splenomegaly was more common among males than females; [Pearson Chi2 (1) = 5.9545, ( Pr = 0.015)]. Patients aged ≤ 20 years were more likely to be in heart failure, [Pearson Chi2 (3) = 8.8255,( Pr = 0.032)], leg swelling more in those with high platelet counts; [Ranksum test, (p = 0.023)]. Unclear presentation was more common in those with high wbc counts; [Ranksum test, (p = 0.015)]. Total wbc counts and BCR-ABL levels were higher among younger patients; [Kruskal-Wallis test (p = 0.036, and 0.025 respectively)]. Patients with leg swelling had lower BCR-ABL levels; [Ranksum test (p = 0.005)], those in heart failure had significantly higher BCR-ABL levels at baseline compared with the rest; [Ranksum test (p = 0.037)]. Patients with lymphadenopathy were more likely to have lower ANCs; [Ranksum test (p = 0.035)]. Conclusions: Clinical manifestations of CML cannot be explained merely by haematologic values. Complex biologic factors should be interrogated further.
Value and expecting of aiding techniques in diagnosis of Meniere′s disease
Authors: Yun Liu
Journal: BMJ (2018)

随着医疗诊断技术的发展，与梅尼埃病诊断相关的辅助检查越来越多，其中主要包括听力学方面的纯音测听、耳蜗电图、甘油试验、听觉脑干诱发电位、耳声发射；前庭功能方面的双温试验、转椅试验、视频头脉冲试验、前庭肌诱发电位等一系列检查，另外还有影像学的钆造影MRI技术。这些辅助中只有纯音测听与梅尼埃病的定性诊断是直接相关的，其他检查研究表明在梅尼埃病中的诊断阳性率各有不同，其中钆造影MRI技术阳性率最高。而前庭功能方面的检查呈现的是某一神经通路上的功能状态，仅靠某一项或几项辅助检查不足以对梅尼埃病进行诊断。
新生儿歪嘴哭综合征10例分析
Authors: 马海侠, 李秀文, 郭纯全, 吴明昌
Journal: BMJ (2007)

分析10例新生儿歪嘴哭综合征患儿的临床资料,均表现为啼哭时病变侧口角无表情而对侧口角下拉,造成不对称的哭泣面或歪嘴哭的面容,但平时或笑脸时面容正常,左右对称.10例中有3例合并先天性心脏病,其中1例合并小头畸形及外耳附件,1例有头顶部局部脱发.本组死亡1例.此征因常合并多种畸形,故应全面检查患儿有无合并的其他畸形。
Study of immune regulatory receptor expression upon combination of chemotherapy and immune checkpoint blockade in a murine lung cancer model.
Authors: James C. M. Ho, Sheng Yan, Sze Kwan Lam
Journal: Journal of Clinical Oncology (2020)

e21083 Background: Blockade of inhibitory immune checkpoints namely the programmed cell death protein 1 (PD-1) and the PD-1 ligand (PD-L1) achieved remarkable clinical outcomes in multiple malignant diseases including lung cancer. However, as the dynamic interactions between the cancer cells and the tumor-associated microenvironment evolves, acquired resistance arises. Thus exploration on alternative strategies would be necessary in order to reach long-term tumor suppression. Methods: Murine lung cancer model was established by inoculation of Lewis lung carcinoma cells subcutaneously on the flank of C57BL/6J mice. Chemotherapy (cisplatin or pemetrexed) or anti-PD-1 alone, or in combination started at 7 days post-inoculation as tumor growth was established. Digital caliper was used to measure tumor sizes and survival rates were recorded. Mice were sacrificed upon humane endpoint (tumor size &gt; 17 mm in diameter). Splenocytes and tumor cells were harvested and expression of immune regulatory markers (including PD-L1, PD-1, Tim-3, OX-40, GITR, LAG-3 and CTLA-4) was analyzed by flow cytometry. Results: While PD-1 blockade delayed tumor growth ( p&lt; 0.001), there was no significant difference in overall survival. Systemically, anti-PD-1 immunotherapy induced upregulation of Tim-3, OX-40 and GITR; cisplatin alone and in combination with anti-PD-1 induced upregulation of GITR; OX-40 is upregulated in combinations of chemotherapy and anti-PD-1. Population of tumor-infiltrating T cells were increased in anti-PD-1-treated mice, while combination of pemetrexed and anti-PD-1 prompted augmented expression of co-stimulatory receptors including GITR and OX-40 within tumor. Conclusions: Cisplatin and pemetrexed triggered different systematic and intratumoral immune responses when used alone or in combination with anti-PD-1 treatment. Increased expression of co-stimulatory receptors in the tumor in response to combination therapy provide insights for investigation of synergism on anti-PD-1 and alternative therapeutic targets.
Effectiveness of lower-dose sexual hormone therapy to prevent bone mineral loss in Chinese postmenopausal women
Authors: Feng-li Wu, Yi-yong Wu, Hong-yan Shi, Yan-chun Li
Journal: BMJ (2008)

Objective To determine the effects of sexual hormone therapy at varied doses on prevention of bone mineral loss in Chinese postmenopausal women. Methods From March 2002 to March 2003, 90 Chinese postmenopausal women were randomly divided into three groups, each given one of the following regiments for 12 months, estradiol valerate (EV) 1 mg plus medroxyprogesterone (MPA) 2 mg for group A (31 subjects), eonjngated estradiol (ethinylestradiol-3-cyclopentylether, CEE) 0.45 mg plus MPA 2 mg for group B (29 subjects) and livial 1.25 mg for group C (30 subjects), respectively. In addition, 400 mg of elemental calcium were given daily to all those women. Bone mineral density (BMD) of the 2nd to 4th lumbar vertebra (L2～4) and biochemical markers of bone turnover, urine N-telopeptide of type Ⅰ collagen/creatinine(NTX/Cr) and serum total alkaline phnsphatase (ALP), were measured before and after drug administration. Results After treatment for 12 months, BMD of the L2～4 increased significantly by 0.039 g/cm2(P 0.05). After treatment for 6 months, urine NTX/Cr reduced from the baseline for all the three groups (P  0.05). After treatment for 12 months, serum ALP significantly reduced from the baseline for all the three groups (P   0.05). Conclusions Sexual hormone therapy at varied doses lower than regular one for 12 months was effective in preventing bone mineral less in postmenopausal women.

Key words: 
Hormone replacement therapy;  Bone density;  Osteoporosis, postmenopausal
Oncology early development technology to facilitate early analysis of safety and efficacy data.
Authors: Mireya Vaca, Louie Naumovski, Chang-Heok Soh, Jailene Leal
Journal: Journal of Clinical Oncology (2020)

e14116 Background: The lack of a standard data review platform for the surveillance of early oncology trials led to the formation of a cross-functional initiative with the objective of creating a data surveillance framework that would provide clinical study teams with access to near real-time data in order to be able to generate fast insights into the safety and efficacy findings of oncology early development trials so that early signal detection or clinical proof-of-concept could take place. Methods: To determine the requirements that would drive the framework, the cross-functional team first conducted user interviews with study physicians to gather information on the types of tables, graphs, and visual outputs that would be most useful to the clinical study team, as well as most useful to re-create as a standard across the early oncology portfolio, focusing at this stage, on solid tumor trials using RECIST 1.1 for the efficacy output. Once these requirements were determined, specification details, including mock-ups of the visual output and guidelines to follow, were created. Programming and development of the pilot dashboard then began using R and Spotfire as the tools of choice. Results: The resulting dashboard branded “OED Fast Insights” included a standard set of pages composed of dynamic tables and graphs organized around 3 components: study disposition, disease response, and treatment-emergent adverse events. The output closely resembled tables and graphs the clinical study team were familiar with through statistical programming output using SAS. However, leveraging the interactive functionality of Spotfire allowed the team to produce dynamic tables and graphs that could be readily filtered by different pre-specified criteria (e.g. cohort, dose level, gender, lines of therapy, best overall response, type of cancer, biomarker status, etc.) or by subject or aggregate-level views, changed by different color indication, or adjusted in other ways by the user. The dynamic aspect of spider plots, waterfall plots, and swimmer lanes were of special interest in identifying early signal detection. Conclusions: The cross-functional initiative began in 2018 and by the end of 2019 the data surveillance framework was successfully scaled and rolled-out to the entire early oncology portfolio of existing trials utilizing RECIST 1.1 solid tumor criteria. The next phase of the initiative will be to extend the framework beyond RECIST 1.1 efficacy surveillance to include hematologic cancers.
Impact of upfront multidisciplinary tumor board (MTB) evaluation on breast sarcoma (BS) outcome.
Authors: Francesco Tolomeo, Giovanna Chilà, Lorenzo D'Ambrosio, Alessandra Merlini, Paola Sgandurra, Franziska Kubatzki, Luca Giuseppe Sgrò, Sara Miano, Giulia Manessi, Alberto Pisacane, Sandra Aliberti, Dimitrios Siatis, Marco Gatti, Nicoletta Biglia, Riccardo Ponzone, Massimo Aglietta, Giovanni Grignani
Journal: Journal of Clinical Oncology (2020)

e23546 Background: Although sarcomas may arise in any site of the body, the intrinsic challenge of BS is to affect the female most frequent cancer site with a completely different and rare set of heterogeneous tumors. Unfortunately, we lack BS-specific prospective trials to precisely guide the clinical decision-making and BS patients are often sent to sarcoma referral centers only after surgery without upfront BS MTB evaluation. Recent evidences reported a significant prognosis improvement with upfront MTB evaluation in retroperitoneal or extremity sarcomas, but whether this strategy might benefit also BS is still not defined. We retrospectively evaluated our prospectively collected database to test whether an upfront MTB evaluation at BS referral centers might impact prognosis and/or the need of subsequent surgeries. Methods: Detailed information on primary surgery, diagnosis, and ≥2 years of follow-up for non-recurring patients were required. We tested the following outcomes: event-free survival (EFS), local EFS (LEFS), distant metastases EFS (DMEFS), overall survival (OS), margin status, subsequent surgeries rate. We evaluated the different outcomes according to upfront MTB evaluation. Kaplan-Meier method was used for survival analyses. Comparisons used hazard ratios (HR). Results: We included 93 patients treated between 1/2000 and 10/2019 at 2 reference BS Centers, median age 53 years (IQR 41-70), ECOG (0;1;2) 67:16:10, high/low grade 60:33. Histotypes were: malignant phyllodes tumor 42 (45%), angiosarcoma 26 (28%), other STS 25 (27%). 27 (29%) cases were considered radiation-induced with a median time from RT of 105 months (IQR 70-127). 44 patients (47%) were discussed upfront in BS MTB, whereas 49 (53%) were not. With a median follow up of 43 months, 5-year EFS, LEFS, DMEFS, and OS for the whole population were 54%, 64%, 60%, and 62%, respectively. LEFS at 5 years had a strong association with margin status (R0 74%; R1 55%, R2 0%, p &lt; 0.001). Regardless of histology, upfront MTB was associated with a significant lower rate of subsequent surgeries (OR 0.16, 0.06-0.41), and with better EFS, LEFS, DMEFS, and OS (HRs 0.57, 0.54, 0.63, and 0.43, respectively). Conclusions: Though retrospective, this series is one of the largest reported to date in BS. Our results highlight the need for early inter-tumor board sharing of BS to take into account sarcoma specificity in the overall disease planning. Given BS rarity, these data will hardly ever be verified in a prospective fashion. Therefore, validation of these results in the Italian Sarcoma Group database is planned.
Similar response rates and survival with PARPi treatments for patients harboring somatic versus germline BRCA mutations: A meta-analysis and systematic review.
Authors: Ghulam Rehman Mohyuddin, Muhammad Aziz, Alec Britt, Lee Wade, Weijing Sun, Joaquina Celebre Baranda, Raed Moh'd Taiseer Al-Rajabi, Anwaar Saeed, Anup Kasi
Journal: Journal of Clinical Oncology (2020)

e16802 Background: PARP inhibitor (PARPi) has recently been approved for various cancers. However, trials have mostly recruited pts with germline BRCA (gBRCA) mutations, and it is unclear whether PARPi have similar efficacy in pts with somatic BRCA (sBRCA) mutations. We aimed to determine the efficacy of PARPi in pts with sBRCA mutations. Methods: Per PRISMA guidelines, systematic review of PubMed, Embase, Cochrane RCT, and Web of Science Collection was performed from inception thru Jan 2020 to identify studies. Our inclusion criteria were clinical trials and retrospective studies that reported use of PARPi in pts with both s and g BRCA mutations. We performed a meta-analysis comparing overall response rate and PFS with PARPi in pts with s versus g BRCA mutations. Results: After screening, 18 studies met our criteria for including both s and g BRCA mutations. Only 8 studies reported response rates for both s and g BRCA mutations (Table). In those studies, 24 out of 43 pts with sBRCA mutations (55.8%), and 69 out of 157 (43.9%) pts with gBRCA had a response to PARPi (pooled OR 1.13, p value = 0.399, I2 = 0). In all five studies that reported PFS, there was no obvious difference in outcomes between sBRCA (HR in these studies ranged 0.23 to 0.27) versus gBRCA (HR ranged 0.17 to 0.27), however a precise statistical analysis could not be done. Conclusions: Our meta-analysis and systematic review of the literature indicates similar outcomes of PARPi therapy in pts with s and g BRCA mutations. Investigation of use of PARPi therapy in a broader patient population, and the inclusion of sBRCA mutations in future clinical trials is essential. [Table: see text]
The impact of therapeutic mediastinal radiation on stent healing in cancer patients: An optical coherence tomography study.
Authors: Jordan Graham, Moez Aziz, Teodora Donisan, Dinu Valentin Balanescu, Nicolas Palaskas, Juan Lopez-Mattei, Mehmet Cilingiroglu, Serban Mihai Balanescu, Nidal M Ganim, Heather Y. Lin, Konstantinos Marmagkiolis, Donald A. Molony, Jean-Bernard Durand, Cezar Iliescu
Journal: Journal of Clinical Oncology (2020)

e19096 Background: Cancer is a prothrombotic and proinflammatory state. Understanding stent healing in cancer patients could modify the approach to antiplatelet regimen and facilitate cancer treatment. Mediastinal radiation therapy brings an additional layer of complexity to an already challenging clinical scenario in cancer patients undergoing percutaneous coronary intervention (PCI). We sought to compare stent healing patterns with and without a history of mediastinal radiation therapy using optical coherence tomography (OCT) data. Methods: All cancer patients that underwent PCI and follow-up OCT less than 12 months post-PCI between 2009-2018 were retrospectively identified from our institutional cardiac catheterization laboratory registry. Stent healing, which was defined by a combination of stent and strut coverage, apposition, expansion, in-stent restenosis, and neo-intimal hyperplasia, was compared among 2 groups of oncological PCI patients: those with and without a history of mediastinal radiation therapy. Differences among the two categories were assessed using linear-effect models. Results: There were 86 cancer patients who received PCI with follow-up OCT within 12 months. Of these, 22% received mediastinal radiation. There was no statistical difference in baseline characteristics (hypertension, dyslipidemia, diabetes, etc.) between the two studied groups. In the non-radiation group, 59% were late stage or advanced cancer patients, while 63% of patients in the radiation group were advanced cancer patients. Stent healing was similar among those who had received radiation therapy and those who had not (Table). Conclusions: A history of mediastinal radiation does not appear to affect early stent healing within 1 year of PCI. Given stent healing appears to be similar with or without radiation, dual anti-platelet therapy regimens may not need to change based on radiation exposure alone. Future studies should address the duration of dual antiplatelet regimens and long-term outcomes (i.e. in-stent restenosis) based on stent healing properties. [Table: see text]
Serine/threonine kinase 11 (STK11) mutations and immunotherapy resistance in patients with non-small cell lung cancer.
Authors: Richie Uba, Luis E. Raez, Katerine Dumais, Frank Gentile, Herman W. Powery, Gelenis Calzadilla Domingo, Paola Izquierdo, Brian Hunis
Journal: Journal of Clinical Oncology (2020)

e15055 Background: There is immune evasion and resistance to checkpoint inhibitors (CPI). Programmed death-ligand 1 (PD-L1) and Tumor mutational burden (TMB) might help us predict response, but we have not yet validated biomarkers that can predict resistance. Mutations (mut) in STK11 can induce epigenetic changes that confer proliferative advantages to cancer cells and preliminary reports have suggested that they can confer resistance to CPI. We investigated the role of STK11 and KRAS mut as markers of poor response to CPI in patients (pts) with non-small cell lung cancer (NSCLC). Methods: Clinical outcomes of 127 pts with stage IIIB-IV NSCLC who were tested for KRAS and STK11 mut and received CPI were evaluated for progression free survival (PFS) and overall survival (OS). For statistical analysis log-rank tests were used to compare OS and PFS, chi-squared tests were used to compare 1-year survivals and proportions among different variables, and Kaplan-Meier survival curves were used to report OS and PFS. Results: Of the 127 pts: 31 had STK11 mut, 14 had STK11+KRAS mut (SKM group), and 10 pts were in the SKMP group (STK11+KRAS mut+PD-L1 (-)). Median age was 65y (27-88y). Males were 54% of the total and 30 pts (24%) were Hispanic (H). STK11 mut patients had an inferior PFS and OS as shown in table. Pts in SKM and SKMP groups had worse outcomes; however, not all the P values were significant. The difference in OS and 1-year OS were very impressive and significant when compared between the SKMP group (4m and 30%) and the wild type group (15m and 73%). There were no significant differences in clinical outcomes for H vs. non-H White pts. Conclusions: The presence of STK11 mut were associated with shorter OS/PFS in NSCLC pts treated with CPIs, proving its utility as a negative predictive marker. This can be enhanced combining STK11 and KRAS mut and possibly adding PD-L1 (-). These findings are consistent with recent studies that have reported STK11 mut as a genomic driver of primary resistance. Due to the small sample size further studies will be needed to validate these findings. [Table: see text]
Correlation of decreased expression of PD-L1 on circulating tumor cells and clinical benefit in SCLC Patients treated with RRx-001, a CD47 downregulator, in a phase II trial.
Authors: Corey Carter, Yusuke Tomita, Akira Yuno, Jonathan Baker, Min-Jung Lee, Sunmin Lee, Scott Caroen, Mary Flanagan Quinn, Bryan Oronsky, Tony R. Reid, Pedro Cabrales, Nacer Abrouk, Jane B Trepel
Journal: Journal of Clinical Oncology (2020)

9062 Background: In a Phase 2 trial called QUADRUPLE THREAT (QT) (NCT02489903), where 2 nd line+ small cell lung cancer (SCLC) patients were treated with RRx-001 and a platinum doublet, the programmed death-ligand 1 (PD-L1) status of circulating tumor cells (CTCs) in 14 patient samples was evaluated. Methods: 26 consented patients received weekly RRx-001 4 mg followed by a reintroduced platinum doublet; epithelial cell adhesion molecule (EPCAM+) CTCs from 10 ml of blood on two consecutive timepoints cycle 1 day 1 and cycle 3 day 8 (cycle duration = 1 week) were detected by EpCAM-based immunomagnetic capture and flow cytometric analysis. CTCs were further characterized for protein expression of PD-L1. Tumor response was classified as partial or complete response based on the response evaluation criteria in solid tumors (RECISTv1.1) measured every 6 weeks. Results: The analyzed clinical data set comprised 14 RECIST-evaluable patients. 50% were females (7/14) and the median age (years) at baseline was 64.5 (Min = 48.5, Max = 84.2, SD = 10.3). The logistic model McFadden goodness of fit score (0 to 100) is 0.477, which is a strong correlation value. The logistic model analyzing the association of CTC PD-L1 expression at two timepoints and response had an approximate 92.8% accuracy in its prediction of clinical benefit (SD/PR/CR). Accuracy is defined in the standard way as 1- (False positive rate + False negative rate). The estimated ROC displayed in Figure 1 suggests a ROC AUC of 0.93 (95% CI: 0.78, 0.99), an excellent measure of performance. Conclusions: Reduction of PD-L1 expression was correlated with good clinical outcome after RRx-001 + platinum doublet treatment. PD-L1 expression reduction in favor of RRx-001 RECIST clinical benefit was clinically significant as compared to non-responders with progressive disease (PD). In the ongoing SCLC Phase 3 study called REPLATINUM (NCT03699956), analyses are planned to correlate response and survival with expression of CD47 and PD-L1 on CTCs. Clinical trial information: NCT02489903.