tbuckley/cabot-search huggingface dataset:
A randomized phase III trial of secondary cytoreductive surgery in later recurrent ovarian cancer: SOC1/SGOG-OV2.
Authors: Rongyu Zang, Jianqing Zhu, Tingyan Shi, Jihong Liu, Dongsheng Tu, Sheng Yin, Rong Jiang, Ping Zhang, Huixun Jia, Yuting Luan, Yuqin Zhang, Xiaojun Chen, Xiao Huang, Wenjuan Tian, Wen Gao, Yanling Feng, Huijuan Yang, Xi Cheng, Yulang Cai
Journal: Journal of Clinical Oncology (2020)

6001 Background: In China, secondary cytoreductive surgery (SCR) has been standard of care in some high volume cancer centers for ovarian cancer (OC) and most pts prefer surgery over the past two decades. Although GOG213 showed no OS benefit, the debate on selected pts and the conflict with certain local clinical care is still open. Methods: Pts with 1st relapsed OC after 6m+ platinum-free interval (PFI) were eligible if predicted to be a potential R0 by iMODEL score combined with PET-CT image and were randomized to SCR followed by chemotherapy (surgery arm) vs 2nd line chemotherapy alone (no surgery arm). Co-primary endpoint is PFS and OS. The 2nd endpoint is accumulated treatment-free survival (TFSa), which was defined as the overall survival time minus the time of surgery and chemotherapy after randomization. We report analysis of PFS and interim analysis of TFSa. Results: 357 pts were randomized 2012-2019. 6.3% of 175 pts were operated in no surgery arm and cross-over rate was 36.9% in 2nd+ relapsed pts of no surgery arm. 97% and 96% of pts received a platinum-containing 2nd line therapy. Complete resection (R0) rate was 76.7% in overall and 61.1% in pts with iMODEL&gt; 4.7. 60 d mortality rates were 0 % in both surgery and no surgery arm. Postoperative 30 d complication rate with ≥ grade 3 was 5.2%. The median follow-up was 36.0 m. Median PFS was 17.4 m and 11.9 m in surgery and no surgery arm, respectively (HR 0.58, 95% CI 0.45-0.74, p &lt; 0.001). Median time to start of first subsequent therapy (TFST) was 18.1 m vs 13.6 m in favor of the surgery arm (HR 0.59, 95%CI 0.46-0.76). 1.1% and 10.1% of pts underwent Bevacizumab and PARPi maintenance in the 2nd line therapy. The OS and TFSa was immatured. The median TFSa was unreached and 39.5 m in R0 subgroup and no surgery arm, respectively (HR0.59, 95%CI 0.38-0.91). TFSa in surgery arm showed a better long-term survival than that in no surgery group (restricted mean survival time from 60 to 72m: 6.2m vs 4.2m). Conclusions: SCR in selected pts resulted in a dramatically significant extension of PFS. The interim analysis of TFSa indicate that SCR might contribute to long-term survival.
Relationship between serum ferritin levels and cardiovascular risk in different genders of Chinese
Authors: Yan Yang
Journal: BMJ (2017)

Objective
To evaluate the association between serum ferritin and the risk of cardiovascular disease among the Chinese population.


Methods
Based on the data from China Health and Nutrition Survey 2009, we used the Framingham risk score to calculate the 10-year risk of cardiovascular disease and analyzed the association between serum ferritin and the risk of cardiovascular disease in different gender by logistic regression analysis.


Results
Among 6 551 respondents, 3 035 (46.3%) were males and 3 516 (53.7%) were females whose mean age were (49.3±13.8) and (49.2±13.7) years, respectively. The median level of serum ferritin was 75.08(36.71-138.75)μg/L. According to the 10-year risk of cardiovascular disease calculated by the Framingham risk score, the low risk group, middle risk group and high risk group were accounted for 79.5%(n=5 207), 15.7% (n=1 028)and 4.8%(n=316), respectively. The median of serum ferritin (121.61 vs. 46.14, P<0.01) and the Framingham risk score (8.6±6.0 vs. 7.3±1.6, P<0.01) of males were higher than those of females. The percentages of the middle risk group (30.6% vs. 2.8%) and high risk group (9.8% vs. 0.5%) of 10-year risk of cardiovascular disease in males were higher than those in females (P<0.01). The 10-year risk of cardiovascular disease ≥ 10% increased with the increasing of serum ferritin in females (trend P<0.01) but not in males.


Conclusion
Serum ferritin levels are positively correlated with the risk of cardiovascular disease in female Chinese.


Key words: 
Ferritin; Cardiovascular diseases; Gender; Framingham risk score
Improved outcomes among breast cancer patients with more frequent mammography screening.
Authors: Ying Liu, Aliza Gordon, Michael Eleff, John Barron, Winnie Chi
Journal: Journal of Clinical Oncology (2020)

e19146 Background: Guidelines for optimal frequency of screening mammography (annual, biennial, never/choice of patient) vary by professional society, due to mixed or insufficient evidence regarding its benefits and harms. Little evidence exists on the impact of screening frequency, rather than any screening, on health outcomes. In this study, we measured differences in cancer stage at diagnosis, treatment rendered, mortality, and cost of treatment for women with different numbers of screenings prior to breast cancer diagnosis. Methods: Utilizing administrative claims, we identified 25,492 women aged 44 or older with various numbers of mammographic screening ≥ 11 months apart during the four years prior to their incident breast cancer diagnosis from 2010 to 2018. Outcomes were assessed during the six months following diagnosis. Regression models were used to compare women with differing numbers of mammograms (0, 1, 2, 3, or 4/5), adjusting for demographic characteristics and baseline comorbidities. Results: More screenings were associated with less advanced cancer at diagnosis, higher rates in lumpectomy and radiation, lower rates in mastectomy and chemotherapy, lower costs and mortality within 6 months post diagnosis (Table). Results were similar in a subgroup with only women aged 44-49 at diagnosis (not shown). Conclusions: Increased frequency of screening mammography is associated with earlier breast cancer stage at diagnosis, less toxic and invasive treatment, lower mortality, and lower cost, including for women under age 50. [Table: see text]
Role of nitric oxide-based immunotherapy in augmenting prostate cancer progression by targeting androgen receptor heterogeneity.
Authors: Himanshu Arora, Anastasia Vedenko, Derek J. Van Booven, Manish Narasimman
Journal: Journal of Clinical Oncology (2020)

e17537 Background: A significant proportion of men with Prostate Cancer (PCa) develop castration resistant prostate cancer (CRPC) and do not respond to hormonal agents that decrease androgens. In trying to understand the causes of androgen resistance that develop in CRPC, it is considered most relevant to study the role of Androgen receptor (AR) in the development and progression of PCa from androgen dependent to androgen independent state. Recent studies have highlighted the significance of tumor microenvironment (TME) in regulation of PCa progression in addition to AR. A key molecule in the regulation of TME interactions is nitric oxide (NO). We have shown in our recent study, the critical association of NO with the TME in CRPC. However, the effects of NO to modulate the progression of PCa to CRPC with respect to AR still remains largely unexplored. Methods: 22RV1, LNCaP, LNCaP APIPC (cells expressing no AR), and LNCaP shAR/pATK (cells expressing low AR), cells were used for the study. Cell proliferation was first assessed by MTT assay. The castrated SCID mice were grafted with 22RV1 cells and were treated with GSNO at the dosage of 10mg/kg/day IP. After treatment, animals were humanely sacrificing. Tumor RNA and proteins were analysed for markers that are important for PCa progression using qPCR, western blot and cytokine antibody array. Animal experiments were carried out in compliance with the IACUC of University of Miami. GraphPad Prism (GraphPad Software) was used for statistical analysis. Results: In addition to reducing the tumor burden, the expression of anti-inflammatory (M2) macrophages (CD206 and Arginase1) is decreased and that of the pro-inflammatory (M1) macrophage (iNOS) is increased in mice which received increased NO levels. Furthermore, to study the effects of NO on progression of PCa from androgen dependent to androgen independent stage, we characterized the LNCAP cell models with differential extent of AR knockdown (LNCaP, LNCaP shAR/pATK and LNCaP APIPC ) for the effects of increased NO levels. Results showed that NO had significant impact on cell proliferation on androgen dependent PCa cells however the effects were negligible in cells expressing low or no AR, suggesting that effects of NO on PCa cell proliferation are AR dependent. Conclusions: Our results suggest that during PCa progression, NO suppresses TAMs to target the TME in an AR dependent manner. Further studies are undergoing to establish the impacts of NO in PCa progression.
液基薄层细胞学检查联合乳管内视镜在乳腺导管癌诊断中的价值
Authors: 张江宇, 张安秦, 王颀, 张佳立, 赖日权, 陈文静, 陈中扬
Journal: BMJ (2007)

对71例疑难性乳头溢液患者术前进行液基薄层细胞学检查(TCT)和联合乳管内视镜(FDS)检查,与术后病理检查结果对照.本组手术后获得病理检查结果的71例(其中57例病变在2级以下导管),FDS诊断导管癌的符合比例为14/18,TCT为12/15,两者联合检测阳性比例为16/18.对于病变发生在2级导管以下者,FDS联合TCT有利于疑难乳头溢液的诊断,提高阳性检出率。
Impact of the affordable care act and early Medicaid expansion on head and neck cancer mortality in the United States.
Authors: Nosayaba Osazuwa-Peters, Justin M Barnes, Jaibir S Pannu, Matthew C Simpson, Sai D Challapalli, Rebecca L Rohde, Eric Adjei Boakye
Journal: Journal of Clinical Oncology (2020)

7035 Background: Medicaid expansion has been associated with increased access to care and earlier stage at diagnosis among patients with head and neck cancer (HNC). However, it is unclear whether Medicaid expansion has impacted HNC mortality rates. We examined the associations between early Medicaid expansions (2010-2011) with mortality rates for HNC in the United States. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program. SEER*Stat was utilized to obtain mortality rates for early expansion (CA, CT, DC, MN, NJ, and WA) and non-early expansion states (all others) in the year ranges as available in SEER: 2005-2007 (pre-expansion) and 2012-2016 (post-expansion). Deaths in 2008-2011 were excluded as a phase-in/washout period. Difference-in-differences analyses were utilized to compare mortality rates pre- and post-early expansion in early expansion vs. non-early expansion states. The parallel trends assumption was tested comparing changes in HNC mortality rates between early expansion and non-early expansion states from 2002-2004 to 2005-2007 and from 2005-2007 to 2008-2011. Results: There were 6882 and 35459 deaths due to HNC in early expansion and non-early expansion states, respectively. HNC mortality rates (deaths per 100,000) decreased from 2005-2007 to 2012-2016 in both early expansion (2.17 to 1.85, difference = -0.32, 95% CI = -0.42 to -0.22) and non-expansion states (2.59 to 2.43, difference = -0.16, 95% CI = -0.22 to -0.11). Relative to non-expansion states, there was a reduction of 0.16 deaths per 100,000 (95% CI = 0.05 to 0.27, p = 0.007) after early Medicaid expansion in expansion states. However, in parallel trends testing, there was no difference in the change in mortality rates between early expansion and non-expansion states from 2002-2011 (p &gt; 0.37). Conclusions: In this quasi-experimental analysis, there was an association between early Medicaid expansion with decreased HNC mortality. Thus, Medicaid expansion might help decrease disparities associated with access to care among HNC survivors. As longer-term data emerges, additional follow-up will be necessary to understand the mechanisms that underlie the HNC mortality benefits seen in early Medicaid expansion.
Selective Mediator dependence of cell-type-specifying transcription
Authors: Martin G. Jaeger, Björn Schwalb, Sebastian D. Mackowiak, Taras Velychko, Alexander Hanzl, Hana Imrichova, Matthias Brand, Benedikt Agerer, Someth Chorn, Behnam Nabet, Fleur M. Ferguson, André C. Müller, Andreas Bergthaler, Nathanael S. Gray, James E. Bradner, Christoph Bock, Denes Hnisz, Patrick Cramer, Georg E. Winter
Journal: Nature Genetics (2020)
西医师使用中成药情况调查及分析
Authors: 贺斌, 曹西军
Journal: BMJ (2012)

调查118名西医师使用中成药的情况,94.9％的医师为患者处方过中成药,其中85.4％按药品说明书使用中成药,64.4％不知道中药之间的配伍禁忌,53.3％不了解中成药的药性,其处方中成药的安全性值得商榷。
CodeBreak 100: Activity of AMG 510, a novel small molecule inhibitor of KRAS<sup>G12C</sup>, in patients with advanced colorectal cancer.
Authors: Marwan Fakih, Jayesh Desai, Yasutoshi Kuboki, John H. Strickler, Timothy Jay Price, Greg Andrew Durm, Gerald Steven Falchook, Crystal S. Denlinger, John C. Krauss, Geoffrey Shapiro, Tae Won Kim, Keunchil Park, Andrew L. Coveler, Pamela N. Munster, Bob T. Li, June Kim, Haby Adel Henary, Gataree Ngarmchamnanrith, David S. Hong
Journal: Journal of Clinical Oncology (2020)

4018 Background: Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation is associated with poor prognosis in colorectal cancer (CRC). AMG 510 is a first-in-class small molecule that specifically and irreversibly inhibits KRAS G12C by locking it in the inactive guanosine diphosphate-bound state. In a previous interim analysis of the phase 1, first-in-human trial of AMG 510, we observed a favorable safety profile and preliminary antitumor activity in patients (pts) with advanced solid tumors harboring KRAS p.G12C. Here, we present updated data in pts with CRC. Methods: Key inclusion criteria were KRAS p.G12C mutation identified through molecular testing, measurable disease, and progression on standard therapy. Primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), as assessed per RECIST 1.1, and overall survival (OS). Oral daily doses of 180, 360, 720, and 960mg were tested in the dose escalation phase, and 960mg dose was selected for the expansion phase. Results: As of Jan 8, 2020, 42 pts with CRC (21 female [50%], median age: 57.5 years [range: 33–82]) were enrolled and dosed (25 on 960mg). All pts received prior systemic therapies; 19 pts (45.2%) received &gt; 3 prior lines. Median follow-up was 7.9 months (mos) (range: 4.2–15.9). 13 pts (31.0%) died, and 8 pts (19.0%) remained on treatment (tx). 22 (52.4%) and 8 (19.0%) pts had remained on tx for more than 3 and 6 months, respectively. Progressive disease was the most common reason for tx discontinuation. 20 pts (47.6%) had tx-related adverse events (TRAEs): 18 (42.9%) had grade 2 or lower TRAEs; 2 (4.8%) had grade 3 TRAEs, which were diarrhea (2.4%) and anemia (2.4%). There were no dose-limiting toxicities, fatal TRAEs, or TRAEs leading to tx discontinuation. Overall, ORR and DCR were 7.1% (3/42) and 76.2% (32/42), respectively. At 960mg, ORR and DCR were 12.0% (3/25) and 80.0% (20/25). 3 pts with PR had duration of response of 1.5, 4.2, and 4.3 months, respectively, and their responses were still ongoing at data cutoff. In all pts treated with all doses, median duration of stable disease was 4.2 mos (range: 2.5[+]–11.0). PFS/OS will be reported. Conclusions: In pts with heavily pretreated KRAS p.G12C mutant CRC, AMG 510 monotherapy was well tolerated, with the majority of pts achieving disease control. Study is ongoing. Clinical trial information: NCT03600883 .
Treatment effects (TEs) of EGFR monoclonal antibodies (mAbs) in metastatic colorectal cancer (mCRC) patients (pts) with KRAS, NRAS, and BRAF mutation (MT) status: Individual patient data (IPD) meta-analysis of randomized trials from the ARCAD database.
Authors: Christos Stelios Karapetis, Heshan Liu, Michael Sorich, Jack Fiskum, Axel Grothey, Eric Van Cutsem, Tim Maughan, Jean-Yves Douillard, Derek J. Jonker, Carsten Bokemeyer, Alberto F. Sobrero, Benoist Chibaudel, John Raymond Zalcberg, Richard Adams, Marc E. Buyse, Aimery De Gramont, Qian Shi
Journal: Journal of Clinical Oncology (2020)

4090 Background: EGFR mAbs have become incorporated into clinical practice for the management of mCRC over the last decade. KRAS and NRAS mutations are used as predictive biomarkers and BRAF V600E mutations are associated with an adverse prognosis. The observed TE within biomarker subpopulations has varied between studies. Methods: IPD from randomized trials with head-to-head comparison between EGFR mAb versus no EGFR mAb (chemotherapy alone or BSC) in mCRC, across all lines of therapy (first, second and later), were pooled. Biomarker subpopulations are defined in the table. Overall survival (OS) and progression-free survival (PFS) were compared between groups by Cox model, stratified by studies and adjusted by age, gender, and performance status. TEs were estimated by adjusted hazard ratio (HR adj ) and 95% confidence interval (CI). Within each biomarker subgroup, EGFR mAb efficacy was explored according to multiple exploratory factors, including line of therapy, type of backbone chemo, gender, sidedness and site of metastasis. Interaction tests were performed. P-values &lt; 0.01 were considered statistically significant to account for multiple comparisons. Results: 5729 pts from 8 studies with data available for ≥ 1 biomarker were analysed. PFS benefits (median 9.2 mos in EGFR mAbs, 8.0 mos in no EGFR mAbs) were confirmed in triple-WT pts, but not for OS (refer to table). No OS/PFS benefits were observed for pts with any of the MT tumors. Exploratory analyses showed a potential detrimental TE of EGFR mAbs in KRAS MT mCRC with liver metastasis (OS: HR adj 1.22, p = .003, p interaction .0056; PFS: HR adj 1.24, p = .0009, p interaction .0008). These results were confirmed within the subgroup of pts with all 3 biomarkers available. Conclusions: This is the largest IPD analysis to explore the predictive value of RAS/BRAF biomarkers in mCRC. Our findings demonstrate that there is no evidence of efficacy of EGFR mAbs in KRAS, BRAF and/or NRAS MT mCRC. EGFR mAbs might have a detrimental effect in KRAS MT mCRC with liver metastases. [Table: see text]
Randomized trial of a collaborative palliative and oncology care intervention to improve communication about end-of-life care in patients with metastatic breast cancer.
Authors: Jennifer S. Temel, Beverly Moy, Areej El-Jawahri, Vicki A. Jackson, Mihir Kamdar, Juliet Jacobsen, Charlotta Lindvall, Jennifer Adrienne Shin, Simone Rinaldi, Heather Carlson, Angela Sousa, Emily J. Gallagher, Samantha Moran, Margaret Ruddy, Maya Anand, Julia Carp, Joseph A. Greer
Journal: Journal of Clinical Oncology (2020)

1008 Background: Studies have demonstrated the benefits of early, integrated palliative care in improving quality of life (QOL) and end-of-life (EOL) care for patients with poor prognosis cancers. However, the optimal timing and outcomes of delivering palliative care for those with advanced cancers that have longer disease trajectories, such as metastatic breast cancer (MBC), remains unknown. We tested the effect of a collaborative palliative and oncology care model on communication about EOL care in patients with MBC. Methods: Patients with MBC and clinical indicators of poor prognosis (N=120) were randomized to receive collaborative palliative and oncology care or usual care between 05/02/2016 and 12/26/2018. The intervention entailed five structured palliative care visits, including a joint visit with oncology when possible, which focused on symptom management, coping, prognostic awareness, decision-making, and planning for EOL. The primary outcome was documentation of EOL care discussions in the electronic health record. Patients also completed questionnaires at baseline and 6, 12, 18, and 24 weeks regarding communication with clinicians about EOL care, QOL, and mood symptoms. Results: The sample included only women (100.0%) who mostly identified as white (87.5%), with a mean age of 56.91 years (SD=11.24). The rate of EOL care discussions documented in the health record was higher among intervention patients versus those receiving usual care (67.2% vs 40.7%, p=0.006), including a higher completion rate of a Medical Orders for Life Sustaining Treatment form (39.3% vs 13.6%, p=0.002). Intervention patients were also more likely to report discussing their EOL care wishes with their doctor compared to usual care patients (OR=3.10, 95% CI: 1.21, 7.94, p=0.019). Study groups did not differ in reported QOL or mood symptoms. Conclusions: This novel collaborative palliative care intervention significantly improved communication and documentation regarding EOL care for women with MBC. Further work is needed to examine the effect of this care model on healthcare utilization at the end of life.
Biomarker testing patterns and trends among patients with metastatic lung cancer.
Authors: Suwei Wang, Hu Huang, Yull Edwin Arriaga, Joseph Tkacz, Anita M Preininger, Metasebya Solomon, Gretchen Purcell Jackson, Irene Dankwa-Mullan
Journal: Journal of Clinical Oncology (2020)

e13667 Background: Guidelines for biomarker testing of metastatic lung cancer patients aid oncologists in making targeted treatment decisions. Despite evidence demonstrating the benefits of genomic and immune biomarker identification in these patients, variations in testing exist. This population-based, retrospective, observational study examined trends in testing rates and timing, assessing associations between testing and patient characteristics, sociodemographic factors, and regional patterns using insurance claims data. Methods: We evaluated patterns of biomarker testing in the IBM MarketScan database between 1/1/2013-12/31/2018. Inclusion criteria consisted of lung cancer patients with an initial diagnosis of metastasis within the study period, continuous insurance coverage from 12 months before to 4 months post-diagnosis, and biomarker testing (EGFR, ALK, ROS1, BRAF V600E, NTRK, PD-L1) within 4 months of diagnosis. Temporal trends were evaluated by the Cochran-Armitage method. Multivariate logistic regression evaluated associations between testing rates and patient-specific factors (i.e., age, gender, comorbid conditions), insurance type, and region (i.e., Northeastern, North central, Southern, and Western) in the United States (US). Results: Of the 8977 patients with metastatic lung cancer, 1040 (12%) had claims for biomarker testing. During the study period, testing rates increased significantly, from 8.4% in 2013 to 20.6% in 2018 (P &lt;.0001); the likelihood of testing increased by year (2014, OR 1.20, 95% CI 0.97 - 1.48 vs. 2018, OR 2.83, 95% CI 2.26 - 3.54). Of patients tested, 25.8% (N = 268) were tested on the day of diagnosis, 70.7 % (N = 735) within 30 days, and 85.6% (N = 890) within 60 days. A lower likelihood of testing was associated with increasing age (OR = 0.97, 95% CI 0.96 - 0.98), enrollment in preferred provider health plans (OR 0.69, 95% CI 0.53 – 0.93), or pre-existing comorbidities of congestive heart failure (OR 0.76, 95% CI 0.59 – 0.98) or diabetes (OR 0.82, 95% CI 0.68 – 0.99). Testing was more likely to occur in females (OR 1.24, 95% CI 1.09 – 1.42), age &lt; 55 years (OR 1.67, 95% CI 1.32 – 2.12) or residence in Northeastern US (OR 1.26, 95% CI 1.05 -1.51). Conclusions: Biomarker testing rates for an insured cohort of metastatic lung cancer patients increased significantly over time, but the likelihood of testing varied based on age, sex, insurance type, comorbidities, and region. Results of this study may inform policy or outreach strategies by highlighting population-based factors influencing biomarker testing rates.