tbuckley/cabot-search huggingface dataset:
Role of immunotherapy in stage IV large cell neuroendocrine carcinoma of the lung.
Authors: Takefumi Komiya, Emily Powell
Journal: Journal of Clinical Oncology (2020)

9060 Background: Despite approvals of immune checkpoint inhibitors in both small cell and non-small cell lung cancers, role of immunotherapy in large cell neuroendocrine carcinoma (LCNEC) in lung is undefined. Methods: Using National Cancer Database (NCDB), Stage IV LCNEC cases diagnosed in 2014-2016 with at least 30-day follow up were analyzed. Clinical demographics included age (20-69 vs. 70+), sex (male vs. female), race (whites vs. others), insurance (uninsured vs. others), institution (academic vs. others), Charlson-Deyo score (0-1 vs. 2-3), brain metastasis (Yes vs. No), liver metastasis (Yes vs. No). Information regarding cancer treatment was limited to first course of therapy, including surgery for primary lesion (Yes vs. No), radiation (Yes vs. No), chemotherapy (Yes vs. No), and immunotherapy (Yes vs. No). Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analyses. A two-sided p-value &lt; 0.05 was considered as significant. Results: Among 661 eligible cases, 37 patients were treated with immunotherapy. No significant association between use of immunotherapy and clinical demographics was observed except for use of chemotherapy (p = 0.0008). Chemotherapy was administered in 34 (92%) and 406 (65%) of cases in immunotherapy and non-immunotherapy groups, respectively. Use of immunotherapy was associated with improved overall survival (Log-rank p = 0.0168). Landmark analysis in the immunotherapy group showed 12 and 18-month survival of 34.0% and 29.1%, respectively, as compared with 24.1% and 15.0% in the non-immunotherapy group Multivariate analysis demonstrated that female sex, presence of liver metastases, surgery, use of chemotherapy and immunotherapy (HR = 0.64, p = 0.0164) had significantly improved survival. Propensity score matching in overall survival showed a nonsignificant trend (p = 0.0733) in favor of immunotherapy group. Conclusions: This retrospective study using one of the largest cancer databases suggests that use of immunotherapy may improve survival of LCNEC patients. Prospective studies are warranted for further validation.
Adjuvant chemoradiotherapy impact on the overall survival of completely resected ampullary and periampullary carcinoma: An updated meta-analysis.
Authors: Philip A. Haddad, Kevin M. Gallagher, Dalia A. Hammoud
Journal: Journal of Clinical Oncology (2020)

4645 Background: Ampullary and Periampullary carcinomas (APAC) are uncommon gastrointestinal cancers that are often amenable to surgical resection. The benefit of postoperative adjuvant chemoradiotherapy (ACRT) in patients with completely resected localized AC has been controversial. A meta-analysis which was conducted in 2017 found no associated survival benefit for adjuvant therapies in APAC. However, this meta-analysis was methodologically flawed and combined studies that used adjuvant chemotherapy alone with those that used ACRT. The purpose of this meta-analysis is to evaluate the impact of ACRT on the overall survival (OS) of patients with completely resected APAC incorporating more recent studies. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of resected Ampullary and Periampullary carcinoma, English language, publications from 1999 to the present, comparative studies reporting OS with hazard ratios (HR) or Kaplan-Meier curves of patients that underwent ACRT versus those that did not, and studies that reported the aggregate OS data of adjuvant therapies where the preponderance of the cohort received ACRT. Adjuvant chemotherapy studies and those that reported aggregate OS for a cohort with preponderance of adjuvant chemotherapy were excluded. A meta-analysis was conducted using an inverse variance method with a random-effects model. Results: Sixteen retrospective series with a total of 1122 patients were included and analyzed. The majority of APAC patients that received ACRT tended to have high risk features. Four of these studies analyzed their OS data for the high risk APAC patients in addition to the cohort as a whole. Intra-arterial chemotherapy and concomitant radiotherapy was used in one study. ACRT was found to be significantly associated with better OS in patients with completely resected APAC (HR 0.76, 95%CI: 0.65-0.88, p &lt; 0.001). Conclusions: This is the first meta-analysis to show that adjuvant chemoradiotherapy is associated with a survival benefit in patients with completely resected high risk Ampullary and Periampullary carcinoma. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of ACRT in this patient population.
Utilization patterns of immune checkpoint inhibitors (ICI) for non-small cell lung cancer (NSCLC) within the veterans health administration (VHA).
Authors: Drew Moghanaki, Renjian Jiang, David Gutman, Abigail Burns, Vidula Sukhatme, William Stokes, Suresh S. Ramalingam, Vikas Sukhatme, Madhusmita Behera
Journal: Journal of Clinical Oncology (2020)

e21630 Background: ICI are used routinely for treatment of lung cancer. We investigated the utilization of PD-1/PD-L1 inhibitors for NSCLC in the VHA. Methods: The VHA Corporate Data Warehouse was queried for data on ICI utilization in NSCLC [IRB #00113521]. The first date of any ICI dispensed was January 6, 2015 and therefore this investigation evaluated all patients diagnosed with NSCLC between 2015 –2019. Results: A total of 27,586 Veterans were diagnosed with NSCLC during the study period with demographics: 76.3% Caucasian, 16.3% black; 97.0% male; median age 71 years. Stage distribution was 27.9%, 7.9%, 15.8%, and 27.0% for stage I, II, III, or IV, respectively. A total of 3,990 patients were identified to have received any ICI, representing 20.1% of patients diagnosed with stage IV; 159 patients received more than one ICI. The median time from stage IV diagnosis to receipt of ICI was 5 months (IQR: 2-9 months). ICI was dispensed in 83.7% for duration of &lt; 1 year, 13.3% for 1-2 years, and 3% for &gt; = 2 years. The median duration of ICI receipt (with IQR in months): Nivolumab = 2.0 (0.5-5.5), Pembrolizumab = 2.1 (0.3-5.9), Durvalumab = 5.1 (1.8-9.2), and Atezolizumab = 0.3 (0.1-2.1). Multivariable analyses demonstrated female, not married, 0 comorbidity, and higher stage (II-IV) were independently associated with shorter time to receipt of ICI. Conclusions: The use of ICI for NSCLC is increasing within this integrated healthcare system and commonly prescribed within 5 months of stage IV diagnosis. Further investigations of this cohort using available clinical, pharmaceutical, and genomic data within the VHA present an opportunity to enhance our understanding of the efficacy of ICI for NSCLC. [Table: see text]
Prognostic role of MRP1 in localized high-risk soft tissue sarcoma (STS): Translational research associated to randomized phase III trial (ISG-STS 1001).
Authors: Javier Martin Broto, David Silva Moura, Rafael Ramos, Luca Braglia, Paola Collini, Salvatore L Renne, Cleofe Romagosa, Jean Michel Coindre, Valerie Velasco, Domenico F Merlo, Emanuela Palmerini, Silvia Stacchiotti, Vittorio Quagliuolo, Antonio Lopez-Pousa, Giovanni Grignani, Jean-Yves Blay, Antonella Brunello, Piero Picci, Paolo Giovanni Casali, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2020)

11543 Background: The ceiling-drug effect seen for most active drugs in STS could be related, partially, to multidrug resistance mechanisms (MDRM). We previously reported the independent prognostic role for RFS and OS of MRP1 in high-risk localized STS of limbs and trunk-wall treated with epirubicin and ifosfamide (Mol Cancer Ther.2014 13(1):249-59). A translational study was carried out within the randomized phase III trial of epirubicin plus ifosfamide vs histotype-tailored neoadjuvant chemotherapy (NCT01710176), to investigate MRP1 prognostic value using the trial population as validation set. Methods: Patients enrolled in the trial were invited to participate, through the informed consent, to this analysis. IHC used QCRL-1 (Santa Cruz biotechnology) MRP1 monoclonal antibody. TMAs were built on the highest-grade area of each tumor, being the procedure blinded for clinical data. MRP1 expression was grouped as low (≤ 25% positive cells) vs high ( &gt; 25% positive cells) expression. For data analysis, patients were grouped as A) epirubicin plus ifosfamide control arm and B) histotype-tailored experimental arm. Drugs used in group B were: gemcitabine-docetaxel (UPS), gemcitabine-DTIC (LMS), trabectedin (High-grade (HG) myxoid LPS), ifosfamide-etoposide (MPNST) and high-dose ifosfamide (SS). Prognostic value of MRP1’s extension was analyzed using Cox’s proportional hazard regression. A p-value &lt; 0.05 was considered statistically significant. Results: 175 patients were analyzed (median age 49; males 61%) with median follow-up of 4.66 y. Group A (n = 88) included HG-myxoid LPS (27%), SS (25%), UPS (24%), LMS (12%) MPNST (10%) and others (2%); group B (n = 87) included UPS (38%), SS (24%), HG-myxoid LPS (20%), LMS (10%) and MPNST (8%). MRP1 high extension was distributed as follows: 48% (A) and 57% (B). High MRP-1 expression showed significantly worse prognosis for disease-free survival (DFS) (HR 2.71 (1.31-5.62) p = 0.007) and a trend towards worse OS (HR = 2.75 (0.97-7.81) p = 0.058) in group A. No correlation was seen between MRP-1 expression and DFS (p = 0.384) or OS (p = 0.665), in group B. Conclusions: MRP1 overexpression was related to significant worse prognosis in 2 prospective randomized series of high-risk, localized, STS treated with neoadjuvant epirubicin and ifosfamide. These agents are both substrate of MRP1; this could add rationale for a possible predictive role, as MDRM, for the two most active drugs in STS. A trial combining epirubicin, ifosfamide and MRP1 inhibitor is currently under design.
偏头痛与抑郁共病
Authors: 杨晓苏, 龙莉莉, 王红星
Journal: BMJ (2010)

偏头痛是一组反复发作的原发性头痛疾病,患病率非常高,近年的流行病学资料显示,偏头痛的全球患病率为10%,终身患病率为14%,严重影响人们的生存质量[1].长期以来,偏头痛被认为与一系列精神障碍性疾病有关,包括抑郁、焦虑、恐怖和惊恐障碍,其中研究最多的是抑郁[2-3]。
Smoking cessation (SC) and lung cancer (LC) outcomes: A survival benefit for recent-quitters? A pooled analysis of 34,649 International Lung Cancer Consortium (ILCCO) patients.
Authors: Aline Fusco Fares, Mei Jiang, Ping Yang, David C. Christiani, Chu Chen, Paul Brennan, Jie Zhang, Ann G. Schwartz, Maria Teresa Landi, Kouya Shiraishi, Brid M Ryan, Hongbing Shen, Matthew B. Schabath, Garcia Adonina, Sanjay Shete, Loic Le Marchand, Angela Cox, Rayjean Hung, Wei Xu, Geoffrey Liu
Journal: Journal of Clinical Oncology (2020)

1512 Background: Tobacco smoking profoundly impacts LC risk; however, data are limited as to what extent SC prior to diagnosis impacts LC overall survival (OS) and lung cancer specific survival (LCSS). LC screening offers a possible teachable moment, but there is uncertainty of SC benefits after a lifetime of smoking. We use the ILCCO database to answer if SC prior to LC dx is associated with better OS and LCSS, considering time since smoking cessation (TSSC). Methods: Using individual data, analysis was performed on 17 ILCCO studies with available TSSC to estimate survival using univariable analysis and models of stage-adjusted and cumulative smoking-adjusted multivariable analysis. Adjusted Hazard Ratios (aHR) from Cox models, cubic spline smooth curves and Kaplan-Meier curves were created. Sensitivity analysis was performed for TSSC and LCSS on 13 studies. Results: Of 34649 patients, 14322 (41%) were current smokers 14273 (41%) ex-smokers and 6054 (18%) never smokers at diagnosis. We confirmed that ex-smokers (aHR 0.88 CI 0.86-0.91) and never smokers (aHR 0.76 CI 0.73-0.8) improved OS compared to current smokers. Amongst ex-smokers, &lt; 2y TSSC (aHR 0.88 CI 0.82-0.94), 2-5y TSSC (aHR 0.83 CI 0.77-0.90) and &gt; 5y TSSC (aHR 0.8 CI 0.76-0.84) had improved OS compared to CS. Sensitivity analysis showed a trend towards improved LCSS survival for &lt; 2y TSSC (aHR 0.95 CI 0.86-1.05) and 2-5y TSSC (aHR 0.93 CI 0.83-1.04), whereas &gt; 5y TSSC significantly improved LCSS by 15% (aHR 0.85 CI 0.78-0.92). To mimic the LC screening participants, in analysis of &gt; 30 pack-years individuals, associations were strikingly strong: &lt; 2y TSSC had improved OS by 14% (aHR 0.86 CI 0.80-0.93); 2-5y TSSC by 17% (aHR 0.83 CI 0.76-0.90); and &gt; 5 TSSC by 22% (aHR 0.78 CI 0.74-0.83), compared to current smokers; for &lt; 30 packs-years, a trend towards better OS was observed for &lt; 2y TSSC (aHR 0.95 CI 0.92-1.02) and 2-5y TSSC (aHR 0.86 CI 0.74-1.01), whereas &gt; 5y TSSC improved OS by 23% (aHR 0.77 CI 0.72-0.82). Conclusions: Among ex-smokers, the risk of overall death was reduced by 12% on &lt; 2y TSSC, 17% on 2-5y TSSC and 20% &gt; 5y TSSC, whereas for LCSS, the benefit was significant only for &gt; 5y TSCC, compared to current smokers at time of diagnosis. Here we demonstrate that convincing screening participants to quit smoking at any point of their trajectory, even just prior to dx such as &lt; 2y TSSC, improved OS, and LCSS benefit was present beyond 5y of quitting. These relationships are independent of pack-years, age, across all stages and other prognostic variables.
A rare family case study of multiple siblings with multiple synchronous primary lung cancers.
Authors: Rui Lin, Tao Wang, Shanshan Xiao, Ruifang Mao, Yue Pu, Hong Liu
Journal: Journal of Clinical Oncology (2020)

e21028 Background: Familial lung cancer is rare, let alone inherited lung cancer with multiple synchronous primary lung cancer lesions. Study of inherited lung cancer may facilitate the understanding of the molecular mechanism of the tumorigenesis. Methods: We identified an extremely rare family of five siblings, four with multiple primary lung adenocarcinomas by pathological examination. DNA samples were extracted from the patient tumor tissues and libraries were prepared for next-generation sequencing (NGS) analysis using a custom 500-gene cancer panel. Results: EGFR L858R or 19DEL mutations were identified in at least one lesion in all of the four lung cancer patients. Interestingly, lung cancer patient L1 had EGFR 19DEL in one lesion and L858R in the other, lung cancer patient L2 had EGFR L858R and KRAS G12C mutation in lesion 1 and lesion 2, respectively. The mutation statuses of EGFR and KRAS were confirmed by ARMS-PCR. The mutational spectrum of the two lesions from the same patient distinguished significantly based on the 500-gene NGS panel analysis, further demonstrating the heterogeneity of cancer mutations. Taken together, these results indicate that patients L1 and L2 both had synchronous primary lung cancers. Due to the small lesions, the two lesions for patient L3 were mixed together; the concurrent EGFR L858R and 19DEL mutations in the tissue sample implicated different drivers in the two different lesions since co-occurring of these two mutations was very rare. For patient L4, EGFR L858R was identified in one lesion and uncommon mutations with low frequencies were observed in the other lesion, consistent with different driving mechanisms for the two lesions. Conclusions: To our knowledge, this is the first study identifying a family of multiple siblings with multiple synchronous primary lung cancers and using NGS to reveal the genetics. Together with germline mutation analysis, this study may shed light on the tumorigenesis of familial lung cancer.
Research status of hyponatremia in cirrhosis with ascites
Authors: 阎振武, 陈建红, 贾德兴
Journal: BMJ (2009)

肝硬化腹水极易发生低钠血症,国外报道的比率在30%左右[1],国内报道约为57%[2].严重的低钠血症常引起或加重肝性脑病、自发性腹膜炎或肝肾综合征,并可直接导致低钠性脑病(即低渗性脑病),低钠血症直接影响患者的治疗与预后,是预测肝硬化腹水早期死亡率的重要指标,越来越受到临床重视,我们就目前肝硬化腹水低钠血症的研究状况综述如下。
Deep learning to distinguish pancreatic cancer tissue from non-cancerous pancreatic tissue: a retrospective study with cross-racial external validation
Authors: Kao-Lang Liu, Tinghui Wu, Po-Ting Chen, Yuhsiang M Tsai, Holger Roth, Ming-Shiang Wu, Wei-Chih Liao, Weichung Wang
Journal: The Lancet Digital Health (2020)

The diagnostic performance of CT for pancreatic cancer is interpreter-dependent, and approximately 40% of tumours smaller than 2 cm evade detection. Convolutional neural networks (CNNs) have shown promise in image analysis, but the networks' potential for pancreatic cancer detection and diagnosis is unclear. We aimed to investigate whether CNN could distinguish individuals with and without pancreatic cancer on CT, compared with radiologist interpretation.In this retrospective, diagnostic study, contrast-enhanced CT images of 370 patients with pancreatic cancer and 320 controls from a Taiwanese centre were manually labelled and randomly divided for training and validation (295 patients with pancreatic cancer and 256 controls) and testing (75 patients with pancreatic cancer and 64 controls; local test set 1). Images were preprocessed into patches, and a CNN was trained to classify patches as cancerous or non-cancerous. Individuals were classified as with or without pancreatic cancer on the basis of the proportion of patches diagnosed as cancerous by the CNN, using a cutoff determined using the training and validation set. The CNN was further tested with another local test set (101 patients with pancreatic cancers and 88 controls; local test set 2) and a US dataset (281 pancreatic cancers and 82 controls). Radiologist reports of pancreatic cancer images in the local test sets were retrieved for comparison.Between Jan 1, 2006, and Dec 31, 2018, we obtained CT images. In local test set 1, CNN-based analysis had a sensitivity of 0·973, specificity of 1·000, and accuracy of 0·986 (area under the curve [AUC] 0·997 (95% CI 0·992-1·000). In local test set 2, CNN-based analysis had a sensitivity of 0·990, specificity of 0·989, and accuracy of 0·989 (AUC 0·999 [0·998-1·000]). In the US test set, CNN-based analysis had a sensitivity of 0·790, specificity of 0·976, and accuracy of 0·832 (AUC 0·920 [0·891-0·948)]. CNN-based analysis achieved higher sensitivity than radiologists did (0·983 vs 0·929, difference 0·054 [95% CI 0·011-0·098]; p=0·014) in the two local test sets combined. CNN missed three (1·7%) of 176 pancreatic cancers (1·1-1·2 cm). Radiologists missed 12 (7%) of 168 pancreatic cancers (1·0-3·3 cm), of which 11 (92%) were correctly classified using CNN. The sensitivity of CNN for tumours smaller than 2 cm was 92·1% in the local test sets and 63·1% in the US test set.CNN could accurately distinguish pancreatic cancer on CT, with acceptable generalisability to images of patients from various races and ethnicities. CNN could supplement radiologist interpretation.Taiwan Ministry of Science and Technology.
Pembrolizumab (pembro) versus standard of care chemotherapy (chemo) in patients with advanced gastric or gastroesophageal junction adenocarcinoma: Asian subgroup analysis of KEYNOTE-062.
Authors: Hironaga Satake, Keun Wook Lee, Hyun Cheol Chung, Jeeyun Lee, Kensei Yamaguchi, Jen-Shi Chen, Takaki Yoshikawa, Kenji Amagai, Kun-Huei Yeh, Masahiro Goto, Yee Chao, Ka-On Lam, Shi Rong Han, Shinichi Shiratori, Sukrut Shah, Kohei Shitara
Journal: Journal of Clinical Oncology (2020)

4523 Background: First-line treatment with pembro or pembro + chemo vs chemo alone was evaluated in patients with PD-L1 combined positive score (CPS) ≥1, HER2-negative advanced gastric cancer in the randomized, active-controlled, phase 3 KEYNOTE-062 study (NCT02494583). We present results from the Asian subpopulation receiving pembro monotherapy or chemo. Methods: Eligible patients were randomly assigned 1:1:1 to pembro 200 mg, pembro + chemo (cisplatin + 5-FU or capecitabine), or placebo + chemo every 3 weeks for ≤35 cycles (~2 years). Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary end points for this analysis were overall survival (OS) in patients with CPS ≥1 and patients with CPS ≥10; progression-free survival (PFS) and objective response rate (ORR) were exploratory end points. Data cutoff was March 26, 2019. Results: Globally, 256 patients received pembro monotherapy and 250 received chemo. Pembro was noninferior to chemo for OS in CPS ≥1 per prespecified margins (median OS, 10.6 vs 11.1 months, respectively; HR [99.2% CI], 0.91 [0.69-1.18]). In the Asian population 62 patients received pembro and 61 received chemo; 26 and 22 had CPS ≥10 (Table). Compared with the global population, Asian patients had a higher proportion of ECOG performance status 0, more diagnoses of stomach cancer, and a greater proportion with 0-2 metastatic sites. Median OS was longer with pembro than chemo using both CPS cutoffs (HR [95% CI]: CPS ≥1, 0.54 [0.35-0.82]; CPS ≥10, 0.43 [0.21-0.89]); 12- and 24-month OS rates were higher for pembro using both CPS cutoffs (12-month OS: CPS ≥1, 69% vs 54%; CPS ≥10, 81% vs 68%; 24-month OS: CPS ≥1, 45% vs 23%; CPS ≥10, 54% vs 27%). The HR (95% CI) for PFS was 1.11 (0.76-1.64) for CPS ≥1 and 0.71 (0.36-1.39) for CPS ≥10. Conclusions: In Asian patients with advanced gastric cancer, OS favored pembro in patients with CPS ≥1 and CPS ≥10. Clinical trial information: NCT02494583 . [Table: see text]
Pediatric cancer registry in Turkey 2009-2019 (TPOG &amp; TPHD).
Authors: M. Tezer Kutluk, Akif Yeşilipek
Journal: Journal of Clinical Oncology (2020)

e22513 Background: The pediatric cancer registry is an essential element of pediatric cancer control. More than 200000 pediatric cancer cases annually are expected in children and adolescents aged 0-14 globally. The current efforts are focusing to improve the survival rates for children and adolescents in LMICs since the survival has already exceeded 80% in most of the high income countries. Here we present the most updated results of the pediatric cancer registry in Turkey. Methods: Pediatric cancer registry has been established by theTurkish Pediatric Oncology Group and Turkish Pediatric Hematology Association in 2002. The childhood cancer cases registered between 2009-2019 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 11 years from 2009 to 2019, 17770 cases were registered. For all cases, median age was 6.8 year (0-17; M/F 9973/7789, 3 hermaphrodite, 5 unknown). Age distribution was 0-4 yrs, 40.3%; 5-9 yrs, 24.0%; 10-14 yrs, 23.6%; 15-19 yrs, 12.1%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (4570, 25.7%, 5.5, 2633/1937); Lymphoma &amp; other RES tumors (3477, 19.6%, 9.9, 2324/1150, 1 hermaphrodite &amp; 2 unknown); CNS [brain &amp; spinal] (2493, 14.0%, 6.9, 1363/1129, 1 unkown); Symphatetic system (1426, 8.0%, 2.4, 743/683); Retinoblastoma (348, 2.0%, 1.5, 204/144); Renal (905, 5.1%, 3.2, 435/469, 1 unknown); Liver (304, 1.7%, 1.8, 172/132); Malignant bone (1209, 6.8%, 12.6, 658/551); Soft tissue sarcomas (1221, 6.9%, 7.5, 703/518); Germ cell (1165, 6.6%, 8.8, 426/736, 2 hermaphrodite, 1 unknown); Carcinoma &amp; other malignant epithelial (533, 3.0%, 13.8, 254/279); Other/non-specific malignant (119, 0.7%, 8.5, 58/61). Five year survival rate was found as 71.9%. Conclusions: The data is the most essential part of the cancer control.This registry has been used widely among professionals since its establishment in 2002. Survival rates for children and adolescents has been improved to 70%. This is at the acceptable level for the income level of Turkey which is classified as an upper middle income country. The registry is a useful source for investigators and decision makers at national and international level.