tbuckley/cabot-search huggingface dataset:
FRACTION-RCC: Innovative, high-throughput assessment of nivolumab + ipilimumab for treatment-refractory advanced renal cell carcinoma (aRCC).
Authors: Toni K. Choueiri, Harriet M. Kluger, Saby George, Scott S. Tykodi, Timothy M. Kuzel, Ruth Perets, Suresh Nair, Giuseppe Procopio, Michael Anthony Carducci, Vincent Castonguay, Edmund Folefac, Chung-Han Lee, Sebastien J. Hotte, Wilson H. Miller, Shruti S. Saggi, David Gold, Robert J. Motzer, Bernard Escudier
Journal: Journal of Clinical Oncology (2020)

5007 Background: The immuno-oncology (I-O) combination nivolumab + ipilimumab (NIVO+IPI) is approved for first-line (1L) and NIVO is approved for second-line treatment post TKI therapy in aRCC. The open-label, randomized, phase 2 Fast Real-Time Assessment of Combination Therapies in Immuno-Oncology (FRACTION-RCC; NCT02996110) platform study has an adaptive design allowing rapid evaluation of I-O therapies, including NIVO+IPI or other investigational combinations. This FRACTION analysis reports preliminary outcomes with NIVO+IPI in aRCC pts after progression on checkpoint inhibitor therapy. Methods: All pts, except 1, had previously received and progressed on checkpoint inhibitor treatment. Pts received NIVO+IPI (NIVO 3 mg/kg + IPI 1 mg/kg Q3W ×4, then after 6 weeks, NIVO 480 mg Q4W), up to 2 years or until progression, toxicity, or protocol-specified discontinuation. Primary endpoints were confirmed objective response rate (ORR; per investigator using RECIST v1.1), duration of response (DOR), and progression-free survival probability at week 24. Safety outcomes were reported. Results: 46 pts were randomized to NIVO+IPI. Pts had 0 (n = 1), 1 (n = 10), 2 (n = 12), 3 (n = 10), or ≥4 (n = 13) prior lines of therapy. All pretreated pts had prior anti-PD-(L)1-, none had prior anti-CTLA-4- therapy, and 37 had prior TKI-based therapy; 45 pts progressed on anti-PD-(L)1 as the most recent therapy. Most pts had clear cell aRCC (n = 44). After a median study follow-up of 8.9 months, ORR was 15.2%; no pts achieved complete response and 7 achieved partial response. DOR ranged from 2–19+ months (n = 7); 5 pts had ongoing response. Six of 7 responders had received ≥2 prior lines of therapy. Any-grade treatment-related adverse events (AEs) were reported in 36 pts (78.3%; fatigue, rash [both 19.6%], and diarrhea [17.4%] were most common). Grade 3–4 treatment-related AEs were reported in 13 pts (28.3%; diarrhea [8.7%], ↑amylase and ↑lipase [both 6.5%] were most common). Treatment-related immune-mediated AEs of any grade were reported in 22 pts (47.8%; rash [19.6%], diarrhea [17.4%], and ↑alanine aminotransferase [8.7%]). No treatment-related deaths were reported. Updated and expanded results with an additional 3 months of follow-up will be presented. Conclusions: These results suggest that NIVO+IPI may provide durable partial response in some pts with prior progression on checkpoint inhibitors, including some heavily pretreated pts. The safety profile of NIVO+IPI in FRACTION pts was similar to historic data in aRCC with this combination. Clinical trial information: NCT02996110 .
Metastasis by semi-quantitative oestrogen receptor expression in stage I-III early diagnosed triple positive breast cancer patients.
Authors: Jasmine Van de Kerkhof, Giuseppe Floris, Christine Desmedt, Annouschka Laenen, Laurence Slembrouck, Kevin Punie, Ann Smeets, Ines Nevelsteen, Els Van Nieuwenhuysen, Caroline G Weltens, Hilde Janssen, Sileny N. Han, Toon Van Gorp, Patrick Berteloot, Ignace Vergote, Hans Wildiers, Patrick Neven
Journal: Journal of Clinical Oncology (2020)

e13031 Background: Some breast cancer subtype-specific demographics and histopathological characteristics can be associated with metastatic outcome. Semi-quantitative oestrogen receptor (sqER) is prognostic in ER-positive HER2-negative tumours. Here, we studied sqER for outcome in early diagnosed triple positive breast cancers (TPBC;ER+/PR+/HER2+). Methods: Retrospective monocentric study of all consecutive early diagnosed TPBC (July 2002 - Dec 2017). Immunohistochemistry (IHC) was used for ER, PR and HER2; IHC ≥1% ER/PR was pos; HER2 was FISH-confirmed. Low sqER was defined as Allred score &lt; 7/8. Local therapy was surgery +/- radiotherapy; systemic treatment was (neo)-adjuvant chemotherapy and trastuzumab and endocrine treatment. The clinicopathological variables we studied apart from sqER were age, menopausal status, BMI, parity, tumor grade and clinical stage at diagnosis. Variables were analysed by a Fishers Exact or Mann-Whitney U test. All reported p-values are two-sided. Cox regression was used to investigate howqER is associated with distant metastasis. Results: We included 415 female patients. 18% had low sqER; these were younger and more likely premenopausal at diagnosis; p &lt; 0.001. Other studied variables didn’t differ by sqER-expression. 7% developed metastasis after a mean follow up of 86 months. High sqER-TPBCs as compared to low sqER-TPBCs were less likely to metastasize (HR 0.42; 95 CI 0.19-0.91). Conclusions: Low sqER in TPBC, present in about a fifth of these tumours, is typically associated with younger age and premenopausal status at diagnosis. Low sqER TPBC are more likely to metastasize when compared to TPBC with high sqER levels. [Table: see text]
Fixing Organ Donation
Authors: Seth J. Karp, Greg Segal, D. J. Patil
Journal: JAMA Surgery (2020)

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Association of snoring with metabolic syndrome in different ethnical populations in Xinjiang Boertala region
Authors: Yan-ying Guo, Xiong Luo, Lei Zhao, Kun Wang, Bing-xian He
Journal: BMJ (2009)

Objective To investigate the association of snoring with metabolic syndrome in Uygur, Kazak, Mongolian, Han ethnical populations of Xinjiang Autonomous Region.Methods The study sample comprised 4107 subjects aged 20-97years including Uygur 1103, Kazak 1019, Mongolian 807, Han 1178 by random cluster sampling from the Xinjiang Boertala region.Snoring status and frequency were collected by questionnaire according to self-reported or family-reported snoring.The metabolic syndrome (MS) was defined by the definition of International Diabetes Foundation (IDF) in 2005.Association of snoring with MS was assessed by comparison the prevalence of MS among the different levels of snoring and the prevalence of moderate-severe snoring among the different component numbers of MS and by test for linear trend and by non-conditional logistic model and by partial correlation after adjustment for potential confounders.Results The prevalence of MS increased with snoring degree increasing, and the prevalence of moderate-severe snoring increased with the component numbers of MS increasing in the four ethnic populations.There was a linear trend between the levels of snoring and the component numbers of MS.After adjustment for age, gender, ethnic, drinking, the risk ratio of MS among moderate-severe snorers as compared to no significant snorers was 2.4 (95% CI2.023-2.803, P=0.000).But the association was lost after controlling for waist circumference and body mass index (BMI) (r=0.019, P=0.227).Conclusions There is a significant association of snoring with metabolic syndrome in the four ethnic populations in Boertala region of Xinjiang.

Key words: 
Snoring;  Metabolic syndrome X;  Epidemiology
Dynamic of time estimation and its relation with levels of distress.
Authors: Nikolay Vladimirov Conev, Martina Ivanova, Eleonora Dimitrova, Asen Yanchev, Ivan Donev
Journal: Journal of Clinical Oncology (2020)

e19091 Background: Our previous study showed a potential relationship between perception of time and level of distress in cancer patients prior to starting chemotherapy. In this study we explored the dynamics of time estimation and the level of distress in cancer patients. Methods: Time estimation and distress were assessed in 262 chemonaïve patients with solid tumors by evaluating each subject’s prospective estimation of how fast one minute passed compared to the actual amount of time passed. The National Comprehensive Cancer Network Distress Thermometer was used at the beginning of the treatment to evaluate the levels of distress. Patients scoring 4 or above were regarded as having high levels of distress. The median value of time estimation was used to stratify the patients into two categories of fast and slow time estimation. After 3 months of treatment time estimation and levels of distress were reevaluated. Results: In total, 125 (response rate 47.7%) patients wanted to be reassessed for the distress level and time estimation. After 3 months of treatment 84 (67.2%) of the patients had not changed their levels of distress, 24 (19.2%) of the patients had low levels of distress, while 17 (13.6%) had high levels distressed. Wilcoxon test did not show a significant change of time estimation and levels of distress before and after 3 months of treatment. We observed a negative weak but significant correlation between the change of distress and change of time estimation (rho = -0.186; p = 0.038). The pattern of the change of time estimation distributions significantly changed according to the reported distress levels at 3rd month. Patients with a fast time estimation at 3rd month had significantly higher levels of distress (4.2±2.6) than patients with a slow time estimation (2.8±2.6). ROC analysis revealed that at the optimal cut-off value of time estimation at 3rd month, high levels of distress can be discriminated with an AUC = 0.64 (95% CI: 0.54-0.73, p = 0.008), a sensitivity of 63.1% and a specificity of 60.1%. Conclusions: Time estimation and its dynamic is a novel potent indicator for high distress in cancer patients.
The relationship between function and thrombosis formation of left atrium appendage assessed by transesophageal echocardiography in patients with nonvalvular atrial fibrillation
Authors: 闫小娣, 朱天刚, 任永凤, 丁茜, 权欣, 王欣, 潘咏梅, 周慧青, 杨松娜
Journal: BMJ (2007)

目的 探讨经食道超声心动图(TEE)检测非瓣膜性心房颤动(房颤)左心耳的大小、功能及与左心耳内血栓形成之间的关系,为临床进行风险评估、判断愈后及指导治疗等提供重要依据.方法 采用TEE对41例非瓣膜性房颤伴或不伴高血压的患者进行左心耳检测,根据左心耳的形态特点,测量出左心耳入口的宽度(d)、左心耳顶部到入口的长度(L),用描记法测出左心耳舒张末期容积(EDV),运用脉冲多普勒测左心耳血流充盈与排空速度,检测左心耳内透声情况及有无血栓.结果 41例房颤患者中左心耳血栓7例(17%),有血栓组与无血栓组的左心耳的大小、容积差异无统计学意义,而左心耳的峰值血流排空速度差异具有统计学意义[(0.52±0.19)m/s与(0.32±0.69)m/s,P＜0.01)];随房颤病程变化,左心耳容积变化具有显著差异[(6.5±1.8)m/s与(8.5±1.0)m/s,P＜0.01];房颤伴高血压组与不伴高血压组间上述指标差异也具有统计学意义[(6.9±2.2)m/s与(7.5±1.2)m/s,P＜0.05].结论 左心耳大小、形态的改变,功能的减低,血流速度的减慢是房颤患者左心耳内血栓形成的重要危险因素,检测左心耳大小、形态及功能对帮助临床进行风险评估、判断愈后及指导治疗等方面有重要的临床价值。
Extensive small cell lung cancer (SCLC) chemotherapy: A population kinetics assessment.
Authors: David J. Stewart, Stephanie Yasmin Brule
Journal: Journal of Clinical Oncology (2020)

e21101 Background: Most progression-free (PFS) and overall survival (OS) curves fit exponential decay models on nonlinear regression analysis (NLRA). Log-linear curve shape varies with tumor &amp; therapy type: straight line vs inflection to right (2 phase decay due to 2 distinct subpopulations with differing sensitivities) vs convex (downward inflection, eg due to stopping therapy that is slowing tumor growth). 1 We compared SCLC to other cancers. Methods: As previously described, 1 we did NLRA of published PFS &amp; OS curves for etoposide-platinum in SCLC. We also assessed various therapies in other cancers. We calculated PFS &amp; OS half-lives and classified curves by log-linear shape. Results: Of 18 evaluable SCLC PFS curves, 14 (78%) were highly convex &amp; 18 (100%) were moderately or highly convex, compared to 35/888 (4%) highly convex &amp; 186 (21%) moderately or high convex curves for other cancers (p &lt; 0.0001). Of 24 evaluable SCLC OS curves, 12 (50%) were highly convex &amp; 24 (100%) were moderately or highly convex, compared to 15/363 (4%) being highly convex &amp; 87 (24%) moderately or highly convex for other cancers (p &lt; 0.0001). In SCLC, 6 vs 4 cycles induction therapy minimally changed PFS half-life (median across studies 5.5 vs 5.2 months, p = 0.27) or OS half-life (9.5 vs 10.4 months, p = 0.06). PFS half-life correlated with OS half-life for other cancers (n 320, Spearman r 0.81, p &lt; 0.0001) but not for SCLC (n 18, r 0.04, p = 0.86). Post progression survival (PPS) correlated positively with PFS half-life for other cancers (n 376, r 0.68, p &lt; 0.0001) but correlated negatively for SCLC (n 18, r -0.43, p = 0.07). SCLC PFS curves had an initial downward inflection at a median of 2.9 months (where 87% of patients are still progression-free), followed by a 2nd inflection point at 4.5 months (where 71% are still progression-free). Median PFS half-life was 14.6 months prior to the 1st inflection point vs 1.9 months after the 2nd inflection point. Our analysis methods 1 suggest that after the 2 nd PFS inflection point, 23% of patients would progress by the next scan if scans are done every 3 weeks, while 40% would progress by the next scan if they are done every 6 weeks. Conclusions: PFS &amp; OS curves for SCLC are more often highly convex than for other cancers since SCLC is sensitive to chemotherapy but progresses rapidly after induction therapy is completed. Giving 6 rather than 4 induction cycles makes no OS difference. New maintenance strategies are needed. Very short PFS half-lives post induction suggest that frequent follow up scans should be done for patients who are candidates for 2 nd line therapy. 1. Stewart. Cancer Med 2019; 8:6871
A national real-world prospective study to assess the effectiveness of adjuvant trastuzumab-dkst in HER2 breast cancer.
Authors: Leandro Ladislau Alves, Lara Lopes Facó, Ana Carolina Cardoso, Alexandre Alcantara, Augusto Theodoro Figueiredo, Rafaella Rodrigues, Fatima Gandufe, Fernanda Cristina Silva, Vivienne Carduz Castilho
Journal: Journal of Clinical Oncology (2020)

e13023 Background: Real-World Evidence (RWE) are gain importance once they are designed to evaluate the effectiveness of drugs whose efficacy has already been demonstrated in randomized controlled trials. In 2017, Brazil approved the first biosimilar of trastuzumab for treatment of breast cancer (BC) with overexpression of HER2. The anti-HER2 treatment significantly improves outcome in patients with HER2-positive BC. Trastuzumab-dkst is clinically effective biosimilar and help to increase access to BC treatment. The aim of this RWE is to address the effectiveness of adjuvant biosimilar trastuzumab-dkst in Brazilian women with early HER2+ BC. Methods: This is a national, multicenter, observational, prospective, RWE study conducted in Brazilian institutions. A hundred and seventy female adult patients, with diagnosis of early stage HER2-positive BC, who received at least one dose of trastuzumab-dkst as adjuvant therapy will be included. The follow-up period will be 5 years after the first dose of trastuzumab-dkst, unless tumor recurrence or death. The safety endpoints are the occurrence adverse events. The effectiveness endpoints are invasive disease relapse-free survival rate at 18, 24, 30 and 36 months after the start of biosimilar use, the invasive disease relapse-free survival after curative-intent surgery and overall survival after curative intent surgery. Given the inexistence of a specific hypothesis to be tested, sample size was based on the accuracy of the two-sided 95% confidence interval (95% CI) for the invasive disease relapse-free survival rate. Results: The recruitment planning covered 21 sites across the five regions of Brazil: North, Northeast, Midwest, Southeast, and South. From those 21 sites, 14 ( &gt; 50%) have already been approved by their local ethical committee for patient recruitment. At 7 months, we have enrolled 50 patients over the five Brazilian regions, which means 29.4% of the total. Conclusions: To conduct RWE in Brazil is still challenging and we have listed 5 possible reasons: (1) there are few RWE studies running in the country, (2) we do not have trialists experienced in RWE design; (3) low medical commitment to adverse event report in RWE; (4) low budget for RWE; (5) slow ethics and regulatory process approval in Brazil. Considering the pioneering and challenges to develop the RWE in Brazil, we are achieving optimum adherence from medical sites. Moreover, roughly one quarter of the target recruitment was reached in the first 7 months after the study start date. Clinical trial information: NCT03892655 .
Is ethnicity related to the distribution of lymphomas by subtype in a majority minority Hispanic community?
Authors: Juan Garza, Adolfo Enrique Diaz Duque, Michelle Janania Martinez, Prathibha Surapaneni, Tyler William Snedden, Sushanth Kakarla, Jeremy Rawlings, David Gregorio, Snegha Ananth, Joel Michalek, Qianqian Liu
Journal: Journal of Clinical Oncology (2020)

e20083 Background: Non-Hodgkin Lymphoma (NHL) continues to be in the top 10 of all cancer related deaths. Discrepancies exist among world regions in lymphoma subtype incidence, with a percentage of DLBCL being higher in Latin America versus Nordic countries. T cell lymphomas (TCL) are reported to be more common in east Asia than in the Western hemisphere.The geographic differences in distribution along with under representation of ethnic minorities across all lymphoma subtypes, establish the basis of our analysis at the only NCI-designated cancer center within a Hispanic (H) predominant patient population. We aim to describe our population diagnosed with Hodgkin Lymphoma (HL) and NHL and compare to known overall global and USA statistics. Methods: Observational study, retrospectively analyzed patients with diagnosis of Lymphoma (HL and NHL). The patients received care at UT Health San Antonio, the biggest Hispanic serving Academic Institution in South Texas, between 2008-2018. Key variables included age, gender, race/ethnicity, stage, treatment received, vitality at 3 and 5 years. Continuously distributed outcomes were summarized with the mean and standard deviation and categorical outcomes were summarized with frequencies and percentages. Primary end point was to characterize distribution of HL and NHL by subtypes in our Cancer Center and compare to North American and overall global distribution. Results: A total of 685 patients with lymphoma were identified. Of the NHL subtypes; DLBCL was the most common identified (209, 31%), (FL) was the most common indolent lymphoma (IL) among all demographic groups (123, 26%), followed by HL (116, 17%) which was more common among non-Hispanic (NH) subgroup (73, 63% vs 42, 36%). Among the TCL, CTCL – Mycosis fungoides was the most common subtype (18, 35%) followed by ALK negative ALCL (12, 24%). Incidence by Gender: The percentage of males (M) was slightly higher vs. females (F) in all subtype lymphoma diagnoses, M (352, 51%), F (333, 49%). M had a higher incidence in DLBCL (108, 52% vs 101, 48%), BL (9, 69% vs 4, 31%), and HL (67, 58% vs 49, 44%). Incidence by Race: Total lymphoid neoplasm rates were higher for H (383, 57%) than NH (293, 43%), other (1, 0.2%), not specified (5, 1%). H had a higher incidence in all subtype lymphomas except for Nodular lymphocyte predominant HL (5, 63% vs 3, 37%). Conclusions: Our Hispanic Hispanic Serving Academic Institution, the distribution of lymphomas doesn’t change when compared with previous reported data. Our population and distribution of lymphoma subtypes are similar to global and USA data.
The mutation of homologous recombination repair genetics is a potential biomarker for immunotherapy in microsatellite stable colon cancer.
Authors: Xueying Wu, Beibei Mao, Henghui Zhang
Journal: Journal of Clinical Oncology (2020)

4076 Background: Patients with microsatellite instability-high (MSI-H) colonic adenocarcinoma (COAD) are always immunotherapy-sensitive for the use immune checkpoint inhibitors, however, the vast majority of COAD patients (85%) are microsatellite stable (MSS). Homologous recombination deficiency (HRD) is demonstrated to be a response predictor to immunotherapies in gynecologic cancers, while limited studies were reported in colon cancer. We focus herein on the mutational pattern of HRR related genes in a large Chinese COAD cohort and further analyze the relationship between HRR-gene mutations and clinical response to immunotherapy in MSS COAD. Methods: The genomic profiling of Genecast cohort which is consisted of 406 Chinese patients with COAD were analyzed in a panel of 543 cancer related genes via next generation sequencing (NGS). The correlation between HRR-gene mutations and tumor immunity or clinical outcome using two COAD genomics datasets (TCGA and MSK-COAD) by the bioinformatic approach. Results: In Genecast Cohort, seventy of 406 (17.2%) patients were identified genomic alterations in HRR-gene, the most frequently mutated genes were ATM (9%), BRCA2 (4%), ATR (3%), RAD50 (3%) and BRIP1 (3%). In MSK-COAD cohort (treated with immune checkpoint inhibitors), HRR-mut group (n = 34) had a significantly better OS than HRR-wt group (n = 50) (log-rank test, P = 0.0087). From the analysis of TCGA cohort, we found that mutations of HRR-gene could increase immune activity in MSS COAD, including increased cytotoxic cells infiltration ( P = 0.035), increased exhausted CD8 T cells infiltration ( P = 0.0098) and higher IFN-g score ( P = 0.03). In contrary, similar results were not found in MSI-H COAD (all P &gt; 0.05). Conclusions: Mutations of HRR-gene could significantly increase immune activity in patients with MSS COAD, implying the feasibility of using HRR-mut as a response predictor of immunotherapy in MSS-COAD.