tbuckley/cabot-search huggingface dataset:
GEM20110714: Final overall survival results of the phase III study of first-line gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma.
Authors: Shaodong Hong, Yan Huang, Yunpeng Yang, Gengsheng Yu, Jun Jia, Jiewen Peng, Qing Lin, Xuping Xi, Peijian Peng, Dongping Chen, Mingjun Xu, Xiaojun Lu, Li Zhang
Journal: Journal of Clinical Oncology (2020)

6521 Background: GEM20110714, the first randomized, phase III study (NCT01528618) of systemic chemotherapy in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC), reported significant reduction of disease progression with gemcitabine plus cisplatin (GP) versus fluorouracil plus cisplatin (FP; hazard ratio [HR], 0.55; 95% CI, 0·44–0·68; P &lt; .001). This study establishes GP as the standard-of-care for first-line treatment of R/M NPC. We present the final overall survival (OS) analysis here. Methods: In this multicenter, open-label study conducted in China, patients who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and R/M NPC were randomly assigned (1:1) to receive up to six cycles of either GP or FP once every 3 weeks. The primary endpoint was PFS, which has been previously reported; OS was a secondary endpoint. The final OS analysis was conducted with the data cutoff date of December 17, 2019. Results: After a median follow-up time of 64.4 months (95% CI, 61.1-67.6), 148 (81.8%) and 165 (91.2%) deaths occurred in the GP and FP arms, respectively. The estimated hazard ratio for OS was 0.723 (95% CI, 0.578 to 0.904; two-sided P = .004). The median OS was 22.1 months with GP versus 18.6 months with FP. The OS probabilities at 1, 3, and 5 years were 79.9% vs. 71.8%, 31.0% vs. 20.4%, and 18.5% vs. 7.6%, respectively. Un-predefined subgroup analyses based on baseline characteristics were consistent with the primary OS analysis. Postdiscontinuation systemic therapy use was similar: GP, 52%; FP, 57%. No new safety signals emerged. Conclusions: In patients with R/M NPC, GP is the first regimen to show significant improvement in OS in a phase III randomized study compared with a traditional chemotherapy regimen (i.e. FP). GP should be considered the standard treatment option for these patients. Clinical trial information: NCT01528618 .
Prevalence and predictors of high-intensity end-of-life care among adolescents and young adults with cancer in Ontario: a population-based study using the IMPACT cohort.
Authors: Hallie Coltin, Adam Rapoport, Chenthila Nagamuthu, Nancy N. Baxter, Paul C. Nathan, Jason D. Pole, Franco Momoli, Sumit Gupta
Journal: Journal of Clinical Oncology (2020)

10559 Background: End-of-life (EOL) care in adolescents and young adults (AYA) with cancer is poorly characterized, though this group may be at risk of elevated rates of high-intensity (HI) care and consequently, increased EOL suffering. Few population-based studies exist, and are limited by incomplete clinical information. AYA care patterns can vary by locus of care (LOC – pediatric v. adult), but LOC disparities in AYA EOL care are unstudied. Methods: We conducted a retrospective decedent population-based cohort study of all Ontario AYA diagnosed between 15-21 years of age with 6 prevalent primary cancers between 1992-2012, who died ≤5 years from diagnosis. Chart-abstracted clinical data were linked to health services data. The primary composite outcome (HI-EOL care) included any of: intravenous chemotherapy ≤14 days from death; &gt; 1 emergency department visit ≤30 days from death; or &gt; 1 hospitalization or intensive care unit (ICU) admission ≤30 days from death. Secondary outcomes included measures of the most invasive (MI) EOL care: mechanical ventilation ≤14 days from death, and death in the ICU. Factors associated with HI-EOL were examined. Results: Of 483 patients, 292 (60.5%) experienced HI-EOL care, 98 (20.3%) were mechanically ventilated ≤14 days from death, and 110 (22.8%) died in the ICU. Patients with hematological malignancies (v. solid tumors) were at greatest risk of HI-EOL care (OR, 2.3; 95CI, 1.5-3.5, p &lt; 0.01), mechanical ventilation (OR, 5.4; 95CI, 3.0-9.7, p &lt; 0.01), and death in an ICU (OR, 4.9; 95CI, 2.8-8.5, p &lt; 0.01). AYA who died in a pediatric center were substantially more likely to experience MI-EOL measures compared to those dying in adult centers (mechanical ventilation, OR 3.2, 95CI 1.3-7.6, p = 0.01). Assessment of interactions showed LOC-based disparities widening over the study period (ICU death in pediatric v. adult centres: early period OR 0.9, 95CI 0.3-2.9, p = 0.91; late period OR 3.3, 95CI 1.2-9.2, p = 0.02; interaction term p = 0.04). AYA living in rural areas were also at higher risk of experiencing mechanical ventilation (OR, 2.0; 95CI, 1.0-3.8, p = 0.04) and death in ICU (OR, 2.1; 95CI, 1.1-4.0, p = 0.02). Conclusions: AYA with cancer experience high rates of HI-EOL care, with patients in pediatric centers and those living in rural areas at highest risk of MI-EOL care. Our study is the first to identify LOC-based disparities in AYA EOL care. Future studies should explore mechanisms underlying these disparities, including potential differences in palliative care services.
Seven-year survival analysis in women with unsuspected uterine malignancy after laparotomic versus laparoscopic hysterectomy: A national claim data retrospective cohort study.
Authors: Jung Hun Lee, Jin-Sung Yuk
Journal: Journal of Clinical Oncology (2020)

e18096 Background: The primary aim of this study was to compare the overall survival of women with unsuspected uterine malignancy (UUM) diagnosed after laparotomic versus laparoscopic hysterectomy for benign gynecological diseases. Methods: A national health insurance database was analyzed from January 2006 to December 2010 to estimate the incidence and mortality of UUM diagnosed after hysterectomy for benign gynecologic diseases using diagnostic and procedure codes. Results: From the database (24 million women annually), 157,232 women were extracted. These women were divided into a laparotomic group (n = 103,631) and a laparoscopic group (n = 53,601). The overall incidences of UUM, unsuspected endometrial cancer, and UUM other than endometrial cancer were 0.65%, 0.46%, and 0.19%, respectively. Women with UUM diagnosed after hysterectomy showed no difference in mean age, incidence of UUM, or socioeconomic status in either group. Kaplan-Meier survival analysis and Cox regression analysis showed that the laparoscopic group was associated with more favorable overall survival than the laparotomic group, especially in UUM other than endometrial cancer ( p &lt; 0.001). Conclusions: In women with UUM diagnosed after hysterectomy for presumed benign gynecological diseases, overall survival up to 7 years favors laparoscopic hysterectomy over laparotomic hysterectomy, and the incidence of UUM is relatively low. However, considering the devastating effect of intraperitoneal dissemination of UUM, surgeons should fully explain this issue to patients preoperatively and try to avoid intraperitoneal spread of tumor cells intraoperatively. [Table: see text]
克拉玛依市维吾尔族和汉族孕妇肝内胆汁淤积症血清生化指标差异与妊娠结局
Authors: 张永红, 付燕燕, 梁新芳
Journal: BMJ (2007)

妊娠期肝内胆汁淤积症(ICP)是产科常见的并发症之一,可导致早产、胎儿窘迫、死胎、死产及新生儿窒息[1],其病因及发病机制不清.关于ICP和民族因素的研究罕见报道,现对我院近5年来收治的160例维、汉族ICP患者临床资料进行回顾性分析。
Analysis of patient attitudes to basic medical services in community health service institutions
Authors: Yan-min Dong, Shu-fen Bian, Yuan-yuan Li
Journal: BMJ (2011)

Objective To collect and analyze patients' evaluation of basic medical services in Tianjin community health service institutions and to suggest improvements. MethodsA total of 15 community health service centers and 15 community health service stations in six urban districts of Tianjin were selected by stratified sampling and 300 randomly intercepted patients were surveyed by questionnaire.Results Approximately half ( 157/300, 52. 3％ ) the patients selected community health service institution as their first choice to seek medical attention. The most important reason for this, with 89.2％ patients responding yes, was that the community health service institution was close to home and very convenient.One quarter (79/300, 25.3％ ) of the patients regularly consulted the same doctor and 17.7％ (53/300)seldom went to see a doctor. The proportion of patients expressing a high degree of satisfaction to service standards and health professionals was 78. 7％, of which satisfaction with physicians' explanation about the patients' illness ranked highest at 83. 7％ (251/300). Patients' confidence level of doctors' diagnosis,physical examination, and auxiliary examination was 92. 0％. Moreover, most (87. 0％ ) patients reported that doctors communicate well with them; 85.0％ (255/300) patients received health instruction from doctors during visits, and 82. 0％ patients reported that doctors pay attention to protecting patients' privacy.The overall satisfaction of patients to environmental facilities and process management of community health service institutions was 73.6％. On the other hand, patient satisfaction with medicine types, service price,instrumentation and equipment, and environment were all lower than the average satisfaction. Conclusions Patients were basically satisfied with medical service in community health service institutions. Three main problem areas were identified: patients' use of community health services is deficient, medical service ability is partially lacking, and the service feature of general practitioners (GPs) is not obvious. Improvements of basic medical service ability in the community, cultivation of GPs, and basic medicine regulation are advocated.

Key words: 
Community health services;  Needs assessment;  Evaluation studies
The impact of locoregional treatment on response to nivolumab in advanced platinum refractory head and neck cancer: The need trial.
Authors: Andrea Botticelli, Silvia Mezi, Giulia Pomati, Paolo Sciattella, Michela Roberto, Alessio Cirillo, Giulia Mammone, Alessandra Cassano, Carmela Di Dio, Alessio Cortellini, Laura Pizzuti, Graziana Ronzino, Massimiliano Salati, Patrizia Vici, Marco Carlo Merlano, Marianna Nuti, Paolo Marchetti
Journal: Journal of Clinical Oncology (2020)

e18508 Background: Immunotherapy is the standard of care in the treatment of platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Previous loco-regional treatment could have an impact on the immune system and response to Nivolumab. The aim of this study is to evaluate the efficacy and safety of Nivolumab in a real world population, identifying the impact of the clinic-pathological characteristics and previous treatment in prediction of early progression. Methods: This is a observational, multicenter retrospective/prospective study including patients (pts) with platinum refractory R/M HNSCC who received Nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity, from October 2018 to October 2019. We analyzed treatment outcomes in term of early progression (within 3 months), clinical benefit, progression free survival (PFS) and overall survival (OS). To determine the influence on outcomes, the following variables were investigated: primary tumor sub-site, age, gender, ECOG, previous loco-regional treatment, previous systemic therapy, metastatic site. Results: Data from 61 pts were reviewed: 15 oral cavity, 14 oropharynx, 7 hyphofarynx, 19 larynx, 6 paranasal sinus. Median age was 66 years (29-82), 48 pts were men. Forty-nine pts (80%) had performance status (ECOG) ≥ 1 at baseline evaluation. Eleven pts (18%) had only loco-regional recurrence, while 50 pts (82%) had one or more metastatic site. 32 (52%) and 17 pts (28%) had smoking and alcohol abuse history, respectively. 44 pts (72%) received surgery followed by adjuvant radiant treatment at standard dose (28, 46%) or concomitant definitive radiotherapy (16, 26%) as upfront treatment with curative intent. With a median follow up of 4 months (range 1-11), early progression occurred in 39 pts during Nivolumab treatment (64%), while clinical benefit (stable disease and partial response) was achieved in 22 pts (36%). No G3-G4 toxicities occurred. Early progression to Nivolumab was significantly associated to previous loco-regional treatment both at univariate and multivariate analysis (p=0.003 and p= 0.04, respectively). Conclusions: Nivolumab in R/M HNSCC is effective and safe even though burdened with a high early progression rate. Loco-regional treatment, including wide neck dissection and high dose radiotherapy, may compromise the efficacy of Nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response.
New potential therapeutic-sequence strategies of TDM1 in the revolutionary era of metastatic HER2-positive breast cancer treatment: A monocentric retrospective experience.
Authors: Maria Vita Sanò, Luisa Castellana, Silvia Caffarelli, Giuseppa Fallica, Maurizio Chiarenza, Marco Ali, Rosanna Dimarco, Di Leo Vita Maria Grazia, Antonio Picone, Rosa Anna Aiello, Domenica Caponnetto, Tiziana Casella, Michele Caruso
Journal: Journal of Clinical Oncology (2020)

e13014 Background: EMILIA study showed benefits in terms of both progression free survival (PFS) and overall survival (OS) administering Ado-trastuzumab emtansine (T-DM1) vs lapatinib-capecitabine in HER2+ mBC patients (pts) treated at least with a previous trastuzumab-taxane-based therapy. However a paucity of data is available on TDM1 efficacy after dual anti HER2 blockade with pertuzumab and trastuzumab (PT). Instead TH3RESA trial revealed the positive impact on OS of T-DM1 also in heavily pre-treated (at least 2 lines of T, lapatinib and taxanes regimens) pts. We conducted a retrospective analysis reporting innovative findings on the sequence of anti-HER2 treatments and how it could be potentially optimized. Methods: Between June 15, 2014 and January 31, 2020 we identified HER2+ (IHC: 3+ or 2+/FISH amplified) mBC pts treated with T-DM1, either as second-line after progression on dual blockade PT (Cohort PT) or after ≤ 3 anti her2-combined regimens (trastuzumab o lapatinib plus chemotherapy) (Cohort T). 74 pts received T-DM1: Cohort T n = 34 (all females, median age = 52,7), Cohort PT n = 40 (39 females, 1 male, median age = 52,2). Within Cohort T: 64,7 % of pts (n = 22) received T-DM1 after 1 previous anti her2-combined regimen, 20,6 % (n = 7) and 14,7 % (n = 5) in third and fourth lines, respectively. Instead, the whole Cohort PT received second line T-DM1 after pertuzumab/trastuzumab. Results: Median progression- free survival was 10,2 in Cohort T and 3,7 months in Cohort PT. As regards the best response rate, 8,8 % (n = 3/34) and 52,5 % (n = 21/40) of pts reported a progressive disease (PD) into the Cohorts T and PT, respectively: stable disease (SD) 38,2 % (n = 13/34) versus 15 % (n = 6/40); partial response (PR) 23,5 % (n = 8/34) vs 15 % (n = 6/40); complete response (CR) 23,5 % (n = 8/34) vs 12,5 % (n = 5/40). Almost 2/3 (n = 21/34) of Cohort T and half (n = 20/40) of Cohort PT pts had a 3+ IHC status. Conclusions: Our data suggest a lower efficacy of T-DM1 after progression on dual HER2-blockade PT. After all, EMILIA trial did not robustly evaluate the role of T-DM1 in this specific subset of pts. Obviously, larger prospective studies are necessary in order to optimize the best sequence strategy in the treatment of metastatic HER2+ BC, in light of the increasingly innovative anti-HER2 agents.
Lipocalin 2 – Devil or Angel? A pan cancer study.
Authors: Vijay Kumar Srinivasalu, Narayana Subramaniam, Manjula Das, Sujan Kumar Dhar
Journal: Journal of Clinical Oncology (2020)

e15609 Background: Lipocalin2 (LCN2, also known as neutrophil gelatinase-associated lipocalin), is a protein that in humans is encoded by the LCN2 gene. It’s abnormal expression serves critical roles in the EMT transition process, angiogenesis, cell migration and invasion in many cancers. We aim to study the expression of LCN2 in tumours with respect to normal and its association with survival in multiple forms of cancer. Methods: On analysis of 23 TCGA datasets containing gene expression data for both tumour and adjacent normal samples, normalized RNAseq RSEM values of LCN2 were compared and differences between median expression levels were assessed using Wilcoxon rank sum test. Effect of LCN2 expression (lowest and highest tertiles) in tumour samples were estimated using Kaplan-Meier survival model. Correlation of LCN2 expression with immune cell population estimated using MCP Counter tool in Colonic Adenocarcinoma (CAC) and Head and Neck Squamous Cell Carcinoma (HNSCC) dataset were assessed. Results: LCN2 overexpression in tumour over normal was seen in 11 cancers viz. CAC, Cholangiocarcinoma, Esophageal ca, Kidney chromophobe, Kidney renal papillary cell ca, HCC, Lung adenoca, Rectum adenoca, Skin cutaneous melanoma, Thyroid ca and endometrial ca whereas LCN2 under-expression in tumour over normal was observed in 4 including HNSCC, Breast invasive ca, RCC and Prostate adenoca. For 8 cancers (Urothelial ca, Cervical and endocervical ca, Glioblastoma, Lower grade glioma, Lung squamous cell ca, Pancreatic adenoca, Phenochromocytoma and Stomach adenoca) no significant difference was observed between normal and tumour samples. LCN2 expression shows hazardous effect on OS in Renal Clear Cell ca (HR = 2.38, p = 0.00027), Glioblastoma (HR = 1.57, p = 0.036) and Pheochromocytoma (HR = 8.03, p = 0.03). On the other hand, high expression of LCN2 shows very mild protective effect on tumour progression in HNSCC (HR = 0.71, p = 0.05) and Prostate ca (HR = 0.46, p = 0.06). In CAC, the normal samples show a correlation between LCN2 expression and T-cells (Pearson r = 0.45, p = 0.0028) and with the T-cell chemo attractant CXCL10 (Pearson r = 0.5, p &lt; 0.0001). Such correlations are broken in tumour samples. In HNSCC no correlations are visible between LCN2 expression and immune cell population estimate in either tumour or normal samples. Conclusions: Literature shows LCN2 as a potential therapeutic target. However, initial analysis of TCGA data fails to establish its role as pro- or anti-tumorigenic in multiple cancers. Further tissue-specific analysis including in vitro and invivo studies are needed to confirm its role in cancer.
A phase I, open-label, multicenter, first-in-human study of the safety, tolerability, pharmacokinetics, and antitumor activity of TPX-0022, a novel MET/CSF1R/SRC inhibitor, in patients with advanced solid tumors harboring genetic alterations in MET.
Authors: David S. Hong, Shiraj Sen, Haeseong Park, Rebecca Suk Heist, Shirish M. Gadgeel, Zachary Franklin Zimmerman, Lyudmila Bazhenova
Journal: Journal of Clinical Oncology (2020)

TPS3663 Background: Alterations in the MET gene, including amplifications, chromosomal translocations, and activating mutations (kinase domain [KD] or exon 14 [Δex14]), occur across various tumors and may function as oncogenic drivers. SRC family kinases function as a key downstream node for MET signaling. CSF1R is a receptor tyrosine kinase associated with tumor progression and suppression of the immune response in the tumor microenvironment. TPX-0022 is a type I kinase inhibitor with a novel macrocyclic structure that potently inhibits MET, CSF1R and SRC to simultaneously target oncogenic MET signaling, its key downstream mediators, and the tumor microenvironment. Methods: This is a multicenter phase 1 first-in-human, open-label study to determine the safety, tolerability, PK, and preliminary efficacy of TPX-0022 in adults with advanced solid tumors harboring genetic alterations in MET. TPX-0022 will be administered orally in continuous 28-day cycles. The primary endpoint is the incidence of DLTs and determination of recommended phase 2 dose (RP2D). Secondary endpoints include ORR by blinded independent central review, intra-cranial response rate, PFS and OS (dose expansion only). In the dose escalation portion, ~30 subjects age ≥18 with solid tumors harboring MET gene amplifications, Δex14, fusions or KD mutations as determined by local tissue-based or liquid biopsy will be enrolled in a 3+3 design. Intrasubject dose escalation will also be allowed. Once the RP2D has been determined, a food effect sub-study will be conducted and ~80 subjects will be enrolled in a dose expansion portion of the study into the following cohorts: I: non-small cell lung cancer (NSCLC) Δex14 (MET therapy naïve), II: NSCLC Δex14 (MET therapy pre-treated), III: MET amplified NSCLC, gastric, or hepatocellular carcinoma, IV: solid tumors with MET KD mutations or fusions. Correlative studies will include analysis of circulating cell-free DNA to identify genomic alterations that may predict activity of TPX-0022 as well as circulating protein biomarkers such as s-MET, HGF, CSF1 and serum cytokines. The study is open and enrolling in the dose escalation portion at the time of submission. Clinical trial information: NCT03993873 .
Clinicopathological characteristics and MYC status determine treatment outcome in plasmablastic lymphoma: a multi-center study of 76 consecutive patients
Authors: Hanno M. Witte, Nadine Hertel, Hartmut Merz, Heinz-Wolfram Bernd, Veronica Bernard, Stephanie Stölting, Nikolas von Bubnoff, Alfred C. Feller, Niklas Gebauer
Journal: Blood Cancer Journal (2020)
Single-institute outcomes of palliative chemotherapy in metastatic head and neck squamous cell carcinoma (HNSCC).
Authors: Rujul H Parikh, Christopher W Fleming, Chandana A. Reddy, Shlomo A. Koyfman, Nikhil Joshi, Neil McIver Woody, Brian B. Burkey, Joseph Scharpf, Robert R Lorenz, Brandon Prendes, Jamie Ku, Eric Lamarre, Larisa Schwartzman, David J. Adelstein, Jessica Lyn Geiger
Journal: Journal of Clinical Oncology (2020)

e18513 Background: Distantly metastatic HNSCC carries a poor prognosis with limited palliative systemic treatment options and a paucity of literature examining factors impacting outcomes of such therapy. We sought to evaluate characteristics conferring more favorable responses to frontline palliative systemic therapy after distant failure (DF). Methods: From an IRB-approved database, we identified 332 pts with metastatic HNSCC treated from 1999 to 2019. Pts with locoregional HNSCC who developed DF and subsequently were treated with palliative systemic therapy were included. Pts were categorized by disease factors, and outcomes were analyzed for progression-free survival (PFS) and overall survival (OS) with Kaplan-Meier curves and log-rank p-values. Results: A total of 85 pts were identified with median age 59.5 years (37-89); 82.4% male, 90.6% Caucasian, 52.9% with &gt; 10 pack-years tobacco use history. Oropharynx primary was the most common site (36.5%) followed by oral cavity (23.5%). All 31 oropharynx cancer pts were HPV-related. Sixty-six pts initially received definitive chemoradiotherapy, with 43 receiving concurrent radiosensitizing cisplatin. Median time to DF was 15 months (m). Thirty pts (35.3%) had concurrent locoregional failure with DF. 62.4% had only one metastatic organ site, with lung-only metastasis in 43.5%. Carboplatin/paclitaxel was the most commonly used frontline palliative chemotherapy (50.6%); 22.4% received frontline nivolumab or pembrolizumab, and 9.4% were treated with frontline platinum/5-FU/cetuximab (9.4%). 63.5% of pts achieved a best response of stable disease or better with frontline therapy. At two years after initial DF, 6 pts (7%) were disease-free. Sixteen pts were alive at last follow-up. After DF, median PFS was 6.5 m and median OS was 10.6 m. On univariate analysis, HPV-related disease was associated with increased PFS (9.5 vs 5.1 m, p &lt; 0.0001) and increased OS (21.1 vs 7.7 m, p &lt; 0.0001). Pts with one metastatic organ site had better OS (11.0 vs 6.2 m, p = 0.047). There was a trend of increased OS with lung-only metastasis (14.4 vs 7.7 m, p = 0.0776), and absence of concurrent locoregional failure (10.8 vs 8.3 m, p = 0.1153). Conclusions: Our results demonstrate that HPV-related metastatic HNSCC is associated with a statistically significant increased PFS and OS. Additionally, there was a trend of increased OS with lower locoregional and distant metastatic burden at DF though statistical significance was not achieved.