tbuckley/cabot-search huggingface dataset:
Clinical experience with the targeted therapy in melanoma patients with brain metastases.
Authors: Natalia V. Zhukova, Rashida Orlova, Nina Antimonik, Natalia P. Beliak, Svetlana Kutukova, Olga Vasyusina, Natalia V. Popova
Journal: Journal of Clinical Oncology (2020)

e22009 Background: According to the clinical studies, the frequency of melanoma brains metastasis reaches 43%, and according to autopsy data, this percentage is even higher - up to 75%. New drugs in clinical practice has significantly improved the prognosis of the metastatic melanoma, however, patients with metastases in the brain are often excluded from large clinical studies, which limits the evidence base of the effectiveness of new therapy methods in this category of patients. Methods: 44 patients with advanced melanoma were treated in SPb Clinical Oncology Dispensary from 2012 till now: 19 male and 25 female, median age is 54y.o. (from 26 to 81). 31 (70%) patients received combination of BRAF and MEK inhibitors, 13 (30%) patients received only BRAF inhibitors. 26 (59%) of patients received target therapy (TT) as 1st line of therapy. Initial performance status (PS) assessed by ECOG scale was following; 8 patient had PS = 0 by ECOG, 29 patients – PS = 1 by ECOG and 6 patients had PS = 2/3 status by ECOG. 8 (18%) patients with brain metastasis has radiation before the TT: 6 patients received at least 1 session of stereotactic radiotherapy and 2 patients underwent radiation of the entire brain. Results: Group of patients without brain metastases: median PFS is 10.0 month (95% CI: 6.0;15.0). The average PFS is 16,90 ± 3,19 month (95% CI:10,64;23,16). Median OS is 15.0 months (95% CI: 11.0;64.0). The average OS is 33,16 ± 5,89 month (95% CI: 21,62 – 44,70). Group of patients with brain metastases: median PFS and OS is not reached. The average PFS is 17,86 +/- 3,3 month (95% CI: 11,42-24,33). The average OS is 20,31 ±2,86 month (95% CI: 14,71 - 25,92). Only 3 from 8 patients have PD after TT on the time of analysis. 5 patients are still alive. Conclusions: Our clinical experience demonstrates comparable efficacy of TT (PFS and OS) in patients with melanoma, regardless of the presence of metastatic brain disease. In the treatment of this category of patients, an integrated approach is very important, including both the use of targeted drugs and the conduct of surgical and radiotherapy. An equally important factor is the rapid onset of treatment.
Plasma next-generation sequencing (NGS) in advanced non-small cell lung cancer (aNSCLC) patients (pts) treated with immune checkpoint inhibitors (ICIs): Impact of <i>STK11</i> and <i>TP53</i> mutations on outcome.
Authors: Alberto Pavan, Elisabetta Zulato, Lorenzo Calvetti, Alessandra Ferro, Giorgia Nardo, Alice Boscolo, Ilaria Attili, Stefano Frega, Alessandro Dal Maso, Giulia Pasello, Valentina Guarneri, Giuseppe Aprile, Pier Franco Conte, Stefano Indraccolo, Laura Bonanno
Journal: Journal of Clinical Oncology (2020)

3046 Background: ICIs revolutionized aNSCLC treatment. The next challenge lays on the search for predictive markers. Detection of multiple tumor-related genetic alterations through NGS in cell free DNA is a promising tool, provided the limited availability of tumor tissue in most cases. Methods: Between January 2017 and October 2019, aNSCLC pts consecutively referring to our Institution were prospectively screened with plasma NGS while included in two clinical trials: VISION (NCT02864992) and MAGIC trial, an observational study. In VISION trial NGS was performed in plasma (Guardant360 test) and tissue (Oncomine Focus Assay). In MAGIC Myriapod NGS-IL 56G Assay was used. Aim of the study was to evaluate the impact of STK11, KRAS and TP53 mutations (muts) on outcome of ICI-treated pts, with overall survival (OS) as primary endpoint. A control group of pts not receiving ICIs was also analyzed. Results: A total of 235 NSCLC pts were enrolled and received ICIs. 93 pts were analyzed in plasma at the time of beginning ICIs: median OS was 18.9 m (95% CI: 13.7-24.1) and median immune-related progression free disease (irPFS) 3.8 m (95% CI: 2.5-5.1). 49 (52.7%), 22 (23.7%) and 8 (8.6%) pts carried TP53, KRAS and STK11 pathogenic alterations, respectively. STK11 mutated pts showed a trend for worse OS compared with wildtype counterpart (14.9 m, 95% CI: 6.5-23.3, versus 20.3, 95% CI: 13.4-27.2, p = 0.192) KRAS muts had no impact on outcome. Pts with TP53 or STK11/KRAS co-mut (n = 3) had worse OS (12.3 m, 95% CI: 9.2-15.4; HR = 3, 95% CI: 1.6-5.8, p = 0.001 and 5.9 m, 95% CI: 1.4-7.6; HR = 2.9, 95% CI: 1.4-6.3, p = 0.007) and worse irPFS (2.8 m, 95% CI: 1.7-3.9, HR = 1.8 95% CI: 1.1-3.1, p = 0.03 and 1.2 m, 95% CI: 0.9-1.5, HR = 2.2 95% CI: 1.2-4.1, p = 0.01). Number of muts negatively impacts pts’ OS (HR = 1.2, 95% CI: 1.1-1.3, p = 0.02) and was higher among TP53 mutated pts (p &lt; 0.001, Mann-Whitney test). In multivariate analysis, TP53 and STK11/KRAS retained significance. A control group of pts not receiving ICIs was analyzed (n = 101): median OS was 16.8 m (95% CI: 13-20.6). Nor STK11 (n = 10), nor STK11/KRAS (n = 6) had impact on OS (HR = 1.8, 95% CI: 0.7-4.7, p = 0.267 and 1.4, 95% CI: 0.7-3.0, p = 0.293) while the presence of TP53 muts (n = 41) was associated with shorter OS (11.4 m, 95% CI: 7.3-15.5; HR = 2.2, 95% CI: 1.2-4.2, p = 0.009). Conclusions: NGS performed in plasma might be used to detect predictive markers. TP53 muts in plasma at baseline had prognostic value, while STK11/KRAS muts were associated with worse outcome to ICIs.
Healthcare disparities and the demand for expanding hereditary breast cancer screening guidelines in African Americans.
Authors: Jordan Alana Ciuro, Samira Ahsan, Alisha Beyer, Nancy Jackson
Journal: Journal of Clinical Oncology (2020)

e13636 Background: The role of predictive genetic testing on cancer care continues to rise in the healthcare community due to increased development, high demand and utilization of multi-panel testing and genome sequencing. BRCA1 and BRCA2 (BRCA1/2) mutations constitute some of the most common, targetable and clinically important markers in breast cancer. Individuals who harbor BRCA1/2 mutation have a substantially increased risk of developing a multitude of cancers, including breast and ovarian cancer. Early detection of these mutations leads to genetic and prevention counselling. The National Comprehensive Cancer Network (NCCN) guidelines recommend BRCA1/2 screening in high risk individuals however has not incorporated differences within ethnic cohorts. Methods: This study reviewed data collected from a genetics clinic in a tertiary community hospital from 2008 to 2018 to analyze the prevalence of BRCA1/2 mutations in various ethnicities as well as identify high risk personal characteristics and family history. A retrospective chart analysis was conducted on 1090 high risk patients seen for genetic counselling for hereditary breast and ovarian cancer syndrome. Results: Among cases, BRCA1/2 mutations were significantly more common in African American when compared to non-Ashkenazi Jewish Caucasians (8.1% vs 3.6%, p = 0.020). African Americans were more likely to have a personal history of any cancer compared to non-Ashkenazi Jewish Caucasians (90.4% vs 84.5 %, p = 0.048). African Americans were also more likely to have personal history of breast cancer compared to non-Ashkenazi Jewish Caucasians (86.4% vs 79.6%, p = 0.048). Regarding family history, there was no significant difference in the prevalence of cancer. Conclusions: In conclusion, we observed a significantly higher rate of BRCA1/2 in the African American population when compared to non-Ashkenazi Jewish Caucasians. Given the documented social barriers such as insurance and lack of knowledge of family history, the prevalence of BRCA1/2 might be underrepresented in literature. It is critical for healthcare providers to assess probability of BRCA1/2 mutations in the African American population and consequently order genetic testing when appropriate. Future studies are needed in this ethnic cohort to establish if a more tailored approach would help identify higher risk individuals.
Evaluation of blood TMB (bTMB) in KEYNOTE-189: Pembrolizumab (pembro) plus chemotherapy (chemo) with pemetrexed and platinum versus placebo plus chemo as first-line therapy for metastatic nonsquamous NSCLC.
Authors: Marina Chiara Garassino, Shirish M. Gadgeel, Delvys Rodriguez-Abreu, Enriqueta Felip, Emilio Esteban, Giovanna Speranza, Maximilian Hochmair, Steven Francis Powell, Edward B. Garon, Rina Hui, Naoyuki Nogami, Razvan Cristescu, Michael Morrissey, Andrey Loboda, Julie Kobie, Mark Ayers, Bilal Piperdi, Maria Catherine Pietanza, Alexandra Snyder, Martin Reck
Journal: Journal of Clinical Oncology (2020)

9521 Background: In a previous analysis of KEYNOTE-189 (NCT02578680), we showed that tissue TMB (tTMB) assessed by whole-exome sequencing was not significantly associated with efficacy in either arm and that pembro + chemo improved outcomes vs placebo + chemo in both the tTMB ≥175 and tTMB &lt; 175 mut/exome subgroups. Here, we explored the association of bTMB with efficacy in KEYNOTE-189. Methods: 616 patients (pts) were randomized 2:1 to pembro + chemo or placebo + chemo. bTMB was assessed in cfDNA using the Guardant Health Omni assay. Association of bTMB (continuous square root transformed) with outcomes in each arm was assessed using Cox proportional hazards models (OS, PFS) and logistic regression (ORR) adjusted for ECOG PS; statistical significance was determined at the 0.05 level without multiplicity adjustment. The clinical utility of bTMB on outcomes was assessed using the cutoff that most closely approximated the 175 mut/exome tTMB cutoff as determined by AUROC analysis. Data cutoff was 21 Sep 2018. Results: 235 (38%) treated pts had evaluable tTMB and bTMB: 160 in the pembro + chemo arm and 75 in the placebo + chemo arm. bTMB as a continuous variable was not significantly associated with OS or ORR for pembro + chemo (one-sided P = .229 and .051) or placebo + chemo (two-sided P = .641 and .069); bTMB was significantly associated with PFS in the pembro + chemo arm (one-sided P = .015) but not the placebo + chemo arm (two-sided P = .058). bTMB and tTMB scores were moderately correlated (r = .61). The bTMB cutoff that most closely approximated tTMB 175 mut/exome was 15 mut/Mb (AUROC 0.81, 95% CI 0.75-0.86). 178 (76%) pts had concordant bTMB and tTMB results—101 low and 77 high by both—whereas 57 (24%) had discordant results—21 high bTMB but low tTMB, 36 low bTMB but high tTMB. Pembro + chemo improved OS, PFS, and ORR vs placebo + chemo for bTMB ≥15 and &lt; 15 mut/exome (Table). Conclusions: Similar to previous findings based on tTMB, bTMB has limited clinical utility in the setting of pembro with pemetrexed and platinum given as first-line therapy for metastatic nonsquamous NSCLC. Clinical trial information: NCT02578680 . [Table: see text]
Effect of general anesthetics on the tumor micro-environment in mouse models of breast cancers of spontaneous metastasis.
Authors: Jun Lin, Ru Li, Yujie Huang
Journal: Journal of Clinical Oncology (2020)

e15503 Background: Metastatic breast cancer is a pressing health concern worldwide. Various treatments have been developed but no significant long-term changes in overall survival are observed. Therefore, there is a demand to improve current therapies to treat this disease. Surgical resection of the primary tumors is essential in the treatment. However, accumulating evidence alludes to a role for volatile anesthetics which are used during the surgery in metastatic tumor development, but the mechanism remains largely unknown. We have shown anesthetics exert different effects on lung metastasis in mouse models of breast cancers. This study analyses the effect of general anesthetics in lung microenvironment associated with the increased metastases. Methods: Balb/c mice and NOD-SCID mice were orthotopically implanted with 4T1 cells and MDA-MB-231 cells respectively, in the mammary fat pad to generate primary tumors. Mice were subjected to the tested anesthetic during implantation and/or before and after surgery. Surgical dissection of primary tumor was performed under anesthesia with sevoflurane or an intravenous anesthetic propofol. Survival curve was constructed and analysed. Mice were euthanized to harvest tissues for histology and cell analysis. Results: As we previously reported, surgical dissection of primary tumor in mice under anesthesia with sevoflurane led to significantly more lung metastasis than with propofol in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. Sevoflurane was associated with increased IL6(Li, Huang, &amp; Lin, 2020). Here we show that anesthesia with sevoflurane resulted in changes of stroma composition in the lung, which was reversed by IL6 pathway interruption. Conclusions: Those results contribute to our understanding of effects of sevoflurane on cancer metastasis and suggest a potential therapeutic approach to overcome the risk of general anesthesia. Li, R., Huang, Y., &amp; Lin, J. (2020). Distinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models. Nat Commun, 11, 642.
Extracorporeal Membrane Oxygenation
Authors: Joseph Hadaya, Peyman Benharash
Journal: JAMA (2020)

Ewan C. Goligher, MD, PhD; George Tomlinson, PhD; David Hajage, MD, PhD; Duminda N. Wijeysundera, MD, PhD; Eddy Fan, MD, PhD; Peter Jüni, MD; Daniel Brodie, MD; Arthur S. Slutsky, MD; Alain Combes, MD, PhD
The role of primary tumor (PT) site as prognostic factor after resection of colorectal (CRC) liver metastases (LM): A mono-institutional cohort study.
Authors: Maria Bensi, Francesco Ardito, Brunella Di Stefano, Maria Vellone, Raffaella Vivolo, Caterina Mele, Marta Ribelli, Elena Panettieri, Floriana Camarda, Alessia Frascarelli, Maria Alessandra Calegari, Michele Basso, Carmelo Pozzo, Felice Giuliante, Giampaolo Tortora, Lisa Salvatore
Journal: Journal of Clinical Oncology (2020)

4081 Background: Radical resection of LM is the only chance of cure for liver-only mCRC pts. Besides the evaluation of technical resectability, several factors must be taken into account for the evaluation of recurrence risk. Among them we should consider the Fong Risk Score and its modified version, including RAS/BRAF status (Brudvik’s score). Tumor sidedness is an important prognostic factor in CRC. The impact of PT site on the outcome of LM resection is still debated. Hence, we retrospectively analysed mCRC pts, underwent to radical LM resection at our Institution, investigating the impact of PT site on DFS and OS. Methods: Liver-only mCRC pts underwent to radical LM resection were included. The association of PT site with DFS and OS was evaluated. The following variables were collected: gender; age (≥ vs &lt; 75 years ); ECOG PS; CEA baseline level; PT site; RAS and BRAF status; mucinous histology; grading (G1-2 vs G3); RECIST response during preoperative treatment; resected PT; synchronous vs metachronous; number of LM; bilobar vs unilobar LM; LM diameter ≥ 5 cm; R0 vs R1 resection. Univariate and multivariate analyses for DFS and OS were performed. Results: A total of 463 liver-only mCRC pts underwent to radical LM resection were included. Seventy (15%) pts had a right-sided (r-s) tumor and 393 (85%) pts a left-sided (l-s) tumor. R-s CRC pts more often had RAS/BRAF mutations in comparison to l-s tumors (76% vs 37%; p &lt; 0.0001). Median DFS and OS was 13.1 and 41.6 months, respectively, in r-s CRC vs 16.0 (p = 0.65) and 62.2 months (p = 0.033), respectively, in l-s tumors. At the multivariate analysis no significant association with survival parameters was shown for tumor sidedness. At the multivariate analysis, R0 resection was independently associated both with better DFS and OS; RAS/BRAF wt CRC and resected PT were significantly associated with improved OS. Considering all wt CRC pts (N = 237), 14 (6%) pts had r-s tumor and 223 (94%) l-s tumor. No significant association of tumor sidedness with survival was shown (DFS r = 10.0 vs l = 16.0 months, p = 0.62; OS r = 40.3 vs l = 66.2 months, p = 0.12). Conclusions: Our results showed that a significant smaller proportion of r-s CRC underwent to radical LM resection, indirectly confirming its worse prognosis. Among radically resected pts, r-s CRC was associated to a shorter OS (significant) and DFS (not significant) compared to l-s CRC, but it was not confirmed at the multivariate analysis. We can conclude that right PT site should not be considered as a contraindication for radical LM surgery, when feasible.
Awareness of community medical staffs with stroke-related knowledge in four cities in China
Authors: Hai-xin Sun, Wen-zhi Wang, Bin Jiang, Sheng-ping Wu, Sheng-yun Chen, Xing-quan Zhao, Yun-hai Liu, Li He
Journal: BMJ (2013)

Objective
To assess the knowledge about stroke among urban community medical staffs in four cities in China.


Methods
Two communities were simple randomly selected from Beijing, Shanghai, Changsha and Chengdu respectively to survey the awareness of community medical staffs with stroke-related knowledge through questionnaires. The questionnaire included: (1) general information, including gender, age and education level, etc; (2) stroke-related knowledge, including stroke risk factors, early symptoms of stroke and other knowledge about stroke prevention.


Results
There were a total of 480 valid questionnaires. The results showed that (1) the awareness percentage of eight stroke risk factors was age 74.4%(357/480), gender 64.0%(307/480), race 64.6%(310/480), family history 77.5%(372/480), hypertension 93.1%(447/480), smoking 81.9%(393/480), diabetes 87.5%(420/480) and dyslipidemia 91.0%(437/480), respectively; (2) Weakness or numbness were the most common symptoms identified by community medical staffs (96.9%, 465/480), and the awareness of dizziness or gait instablity was the lowest (79.0%, 379/480); (3) the stroke knowledge score was affected by education level (t=5.808, P<0.01) and age (t=2.217, P=0.027).


Conclusion
The cognitive level of community medical staffs with stroke-related knowledge requires further improvement in four cities in China. And the targeted educational population should be directed at those who are of lower education level and young.


Key words: 
Stroke; Knowledge; Community medical staffs
Research progress of lung cancer complicated with venous thrombosis
Authors: Siying Hu, Yiping Han
Journal: BMJ (2018)

Lung cancer and venous thrombosis(VTE)are two conditions that frequently cause death and disability. Recent studies have shown that lung cancer patients have high incidence of VTE, which would lead to poor prognosis. This article summarizes the research progress in the epidemiology, mechanism, clinical characteristics and risk factors of complicated venous thrombosis in lung cancer patients, and provides information for its diagnosis, prevention and treatment.


Key words: 
Lung neoplasms; Venous thrombosis; Pulmonary embolism
Integrated geriatric assessment and treatment (INTEGERATE) in older people with cancer planned for systemic anticancer therapy.
Authors: Wee-Kheng Soo, Madeleine King, Alun Pope, Phillip Parente, Peteris Darzins, Ian D. Davis
Journal: Journal of Clinical Oncology (2020)

12011 Background: Older people experience significant adverse effects of cancer and anti-cancer therapy due to age-related vulnerabilities, including medical, functional, cognitive, nutritional and psychosocial issues. Comprehensive geriatric assessment and management (CGAM) provides a powerful framework to assess an older person’s health status and offers a coordinated, person-centered approach to care. Despite its effectiveness, the uptake of CGAM in oncology has been limited due to a lack of randomized evidence in this setting. This study evaluated the effectiveness of CGAM in older people with cancer. Methods: INTEGERATE is a prospective, randomized, parallel group, open-label study in patients aged &gt;70 years with cancer planned for chemotherapy, targeted therapy or immunotherapy. Patients were randomly assigned (1:1) to receive either geriatrician-led CGAM integrated with usual care (integrated oncogeriatric care) or usual care alone, using minimization to balance treatment intent, cancer type, age, sex and performance status. Health-related quality of life (HRQOL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-ELD14 at 0, 12, 18 and 24 weeks. The primary outcome was HRQOL measured by the validated Elderly Functional Index (ELFI) score. Major secondary outcomes included function, mood, nutrition, health utility, treatment delivery, healthcare utilization and survival. Results: Of the 154 patients who underwent randomization, 13 died by week 12 and 130 (92.2% of the remaining patients) completed at least two primary outcome assessments. For the primary outcome, patients in the intervention group had significantly better ELFI score than the usual care group across all followup timepoints, with a maximal difference at week 18 (estimated marginal mean ELFI score 72.0 vs 58.7, p= 0.001). In addition, significant differences favoring the intervention group over the usual care group were seen in HRQOL (domains: physical, role and social functioning; mobility, burden of illness and future worries), unplanned hospital admissions (-1.2 admissions per person-years, p&lt; 0.001) and early treatment discontinuation (32.9% vs 53.2%, p = 0.01). Conclusions: Integrated oncogeriatric care led to improvements in HRQOL, unplanned hospital admissions and treatment discontinuation in older people receiving systemic anti-cancer therapy. Older people (&gt;70 years) planned for anti-cancer therapy should receive CGAM to optimize their clinical care and health outcomes. Clinical trial information: ACTRN12614000399695 .
缺铁性贫血的再认识
Authors: 陈嘉林
Journal: BMJ (2007)

缺铁性贫血(IDA)是最常见的贫血性疾病之一.据WHO 1985年报告,全球约5～6亿人口患有IDA.我国月经期妇女IDA的发病率约11%～12%;成年男性和绝经后妇女IDA的发病率约2%～5%[1,2].因此,IDA是内科医师,特别是社区全科医师经常面临的问题。