tbuckley/cabot-search huggingface dataset:
Will oncologists and patients make trade-offs between efficacy and toxicities in first-line treatment of advanced HER2 negative breast cancer?
Authors: Suvina Amin, Sara M. Tolaney, M. Janelle Cambron-Mellott, Kathleen Beusterien, Martine C. Maculaitis, Leonard Kusdra, Emily Mulvihill, Reshma Shinde, Kimmie McLaurin
Journal: Journal of Clinical Oncology (2020)

e19228 Background: Treatment options for HER2- metastatic breast cancer (mBC) have greatly increased with the approval of new agents in the first-line (1L) setting: CDK4/6 inhibitors, PARP inhibitors, and atezolizumab. This study evaluated which treatment attributes patients (PTs) and oncologists (ONCs) prioritize in triple-negative and hormone-ineligible HR+/HER2- mBC PTs. Methods: US PTs with HER2- mBC, recruited via advocacy groups, and ONCs, recruited via a healthcare research panel, completed an online, cross-sectional survey. Preferences were assessed via a discrete choice experiment, where participants selected between hypothetical treatment profiles with varying attribute levels associated with 1L mBC therapies; attributes were developed through prior qualitative research with PTs and ONCs. Hierarchical Bayes was used to estimate attribute-level preference weights. Results: PTs (N=169; 69% triple-negative, 30% HR+) averaged 54 years old; treatment history included chemotherapy (92%), hormone therapy (35%), CDK4/6 inhibitor or mTOR inhibitor (24%), and immunotherapy (2%). ONCs (N=117) averaged 16 years in practice; 78% practiced in a community setting. Improving overall survival (OS) by 15 months was most important to PTs and ONCs and was at least twice as important as each of the other attributes (Table). All grade neuropathy was more important to ONCs than PTs; all grade nausea, alopecia, and grade 3/4 immune-related adverse events (AE) were more important to PTs than ONCs. Most ONCs (81%) reported that PTs prefer an oral therapy over IV; 51% of PTs agreed and 25% neither agreed nor disagreed. In the context of treatment goals, ONCs (67%) perceived that PTs are more focused on efficacy than quality of life (QoL); fewer PTs (29%) agreed. Conclusions: PTs and ONCs are willing to make trade-offs between efficacy and toxicities. However, PTs place higher value than ONCs on toxicities impacting QoL while aiming to increase survival. [Table: see text]
替罗非班致急性极重度血小板减少一例
Authors: 费民忠, 魏勇, 欧阳平, 杨婉花
Journal: BMJ (2011)

患者男性,75岁,因持续性胸痛6 h就诊.平素无明显胸闷、胸痛.否认高血压、糖尿病,否认特发性血小板减少性紫癜、再牛障碍性贫血、自身免疫性疾病等病史,否认吸烟史,否认药物过敏史,否认高血压、冠心病和糖尿病等家族史.急查心电图示急性广泛前壁心肌梗死;心肌酶:肌酸激酶2000 U/L,肌酸激酶同工酶262 U/L,肌钙蛋白I(TNI)5.53μg/L;血常规:白细胞12.2×109/L,血红蛋白171 g/L,血小板142×109/L;凝血功能:凝血酶原时间(PT)13.4 s,部分凝血活酶时间(AFTT)31.7 8,D-二聚体0.6 mg/L;生化:ALT 31 U/L,肌酐57μmol/L。
CD8A and HAPLN3 expression profiling to reveal an immunologic subtype of bladder cancer with favorable survival.
Authors: Jingjiao Ma, Ning He, Jianfei Wang, Lingyu Wang, Ge Jin, Rongbo Lin, Yadong Yang
Journal: Journal of Clinical Oncology (2020)

e15193 Background: At present, immune checkpoint inhibitors (ICI) have demonstrated robust anti-tumor activity with a favorable safety in bladder cancer (BLCA). However, less than half of BLCA patients respond to immunotherapy. We aimed to further delineate the immunologic subtype of BLCA to pick patients who might benefit from ICI treatment. Methods: The RNA-seq and clinical data were collected from The Cancer Genome Atlas (TCGA) data portal (n = 408) and Gene Expression Omnibus (GEO) (GSE48075, n = 142; GSE32894, n = 308). TCGA and GSE48075 cohort are the discovery datasets, and GSE32894 cohort is used for validation. According to the expression of every specific gene ( Gi), patients were divided into two groups using median FPKM as cutpoint value, namely G i _high and G i _low, respectively. Combined with CD8A expression, all the patients were divided to four groups as follows: CD8A_high/ G i _high, CD8A_high/ G i _low, CD8A_low/ G i _high, and CD8A_low/ G i _low. Then we calculated the pearson correlation coefficients between G i and 13 immune checkpoint genes ( CD274, IDO1, CTLA4, LAG3, CD276, VTCN1, CD70, HAVCR2, CD40, CD47, TNFRSF18, TIGIT, and TNFSF14). Overall or disease free survival of the four groups were compared using the survfit function from the survival R package and P values from log-rank tests were reported. Results: In the discovery cohort, we found CD8A_high/ HAPLN3_low group showed the best overall survival, whereas the CD8A_low/ HAPLN3_high showed the worst (TCGA, p = 0.013; GSE48075, p = 0.012). Additionally, HAPLN3 was positively correlated with 5/13 immune-checkpoint genes: CD274, IDO1, CTLA4, LAG3, HAVCR2 (r &gt; 0.6, p &lt; 0.01). And the same observations were extended in the validation cohort (GSE32894): CD8A_high/ HAPLN3_low group exhibited a favorable survival (p = 0.00059), and HAPLN3 had a strong correlation with the same 5 immune-checkpoint genes (r &gt; 0.6, p &lt; 0.01). Conclusions: The combination of high CD8A and low HAPLN3 expression identified a subtype of BLCA patients with favorable survival and these findings may further help refining the selection of BLCA patients for immunotherapy.
Cost-effectiveness of first-line therapy for advanced renal cell carcinoma in the immunotherapy era.
Authors: Divya Ahuja Parikh, Paul Irvin Serrato, Sandy Srinivas, Tess Sophie Ryckman, Joshua Salomon, Jeremy D Goldhaber-Fiebert
Journal: Journal of Clinical Oncology (2020)

e19392 Background: The treatment landscape for advanced renal cell carcinoma (RCC) has transformed in the past two years. Both Nivolumab plus Ipilimumab and Pembrolizumab plus Axitinib are approved regimens for first-line treatment of intermediate to poor-risk patients with advanced RCC. The choice between these immunotherapy-based combinations for first-line therapy is highly debated; no prior study has evaluated the cost-effectiveness of both combinations compared to Sunitinib. Methods: We used a decision analytic Markov model informed by the recent Checkmate-214 and Keynote-426 phase 3 randomized controlled clinical trials to evaluate costs and effectiveness of Nivolumab plus Ipilimumab, Pembrolizumab plus Axitinib, and Sunitinib in the first-line treatment of advanced RCC from a US health payer perspective. We used the model to extrapolate survival beyond the closure of the trials and examined the robustness of our findings with sensitivity analyses. Main outcomes were life expectancy, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios, all discounted at 3% annually. Results: Nivolumab plus Ipilimumab increased life expectancy by 0.58 years at cost of approximately $190,000 per QALY gained compared to Sunitinib. Pembrolizumab plus Axitinib increased life expectancy by 0.39 years at a cost of approximately $861,000 per QALY gained compared to Nivolumab plus Ipilimumab. The results were not sensitive to reasonable changes in drug costs and quality of life estimates. Both combinations cost more than the traditional willingness-to-pay threshold (WTP) of $150,000 per QALY gained. A 20% price reduction is required for Nivolumab and Ipilimumab to be cost-effective and a 48% price reduction is required for Pembrolizumab plus Axitinib to be cost-effective. Conclusions: Both Nivolumab plus Ipilumumab and Pembrolizumab plus Axitinib provide increased longevity and reduced morbidity relative to Sunitinib. However, the prolonged duration of treatment and doublet-drug pricing results in high-costs. Price reductions are required for both of the immunotherapy-based combinations to be cost-effective. [Table: see text]
Impact of human papillomavirus (HPV) infection on the outcome of perioperative treatments for penile squamous-cell carcinoma (PSCC).
Authors: Patrizia Giannatempo, Marco Bandini, Yao Zhu, Dingwei Ye, Antonio Augusto Ornellas, Nick Watkin, Michael Ager, Oliver W. Hakenberg, Axel Heidenreich, Daniele Raggi, Friederike Haidl, Laura Marandino, Filippo Pederzoli, Alberto Briganti, Francesco Montorsi, Juan Chipollini, Mounsif Azizi, Maarten Albersen, Philippe E. Spiess, Andrea Necchi
Journal: Journal of Clinical Oncology (2020)

5088 Background: PSCC patients (pts) with palpable inguinal lymph node (ILN) disease have a poor overall survival (OS). Multimodal perioperative treatments are usually offered despite the lack of clinically meaningful efficacy. Pending the availability of novel effective systemic therapy, the optimization of conventional treatments in better selected pts is needed. Methods: Within an international, multicenter database of 924 PSCC pts who received ILN dissection from USA, Europe, Brazil and China, 494 had information on HPV, and 52 (10.5%) had HPV+ PSCC, predominantly assessed with immunohistochemistry (53%). Multivariable logistic regression analyses evaluated the association between pt factors and HPV status. Multivariable Cox analyses (MVA) assessed predictors of overall mortality (OM), including HPV status, pathologically-involved ILN ratio (ILNR), extranodal extension, margin status, vascular invasion (VI), perioperative RT (pRT) and perioperative chemotherapy (pCT). Comparisons between HPV status and ILNR were performed using interaction tests. Kaplan-Meier method was used to define the OS benefit related in HPV-stratified sub-groups. Results: Median age at diagnosis was 58yrs. Overall, pCT and pRT were used in 227 (46%) and 50 (10%) pts. The median follow-up was 62 months. Neither clinical factors nor country were associated with HPV status. On MVA, ILNR (HR:1.01, p = 0.01) and extranodal extension (HR: 1.5, p = 0.02) were statistically significantly associated with OM, but HPV was not (p = 0.2). However, in the subgroup of pts who received pRT, HPV status was associated with favorable OM (HR: 0.11, 95%CI: 0.03-0.5, p = 0.004) together with negative VI (p = 0.03), and the use of adjuvant CT (p = 0.04). A significant interaction was found on OM between HPV+ status and increasing ILNR, with a cutoff at 50% (p = 0.05). Results are limited by their retrospective nature and small numbers in each subgroup. Conclusions: In the largest available dataset of ILND for PSCC, we observed that pRT seemed to be more effective in the subgroup of HPV+ PSCC. These results should be considered as hypothesis-generating and may inspire both the future prospective trials or the ongoing InPACT study.
Improvement in lung cancer survival: Six-year survival analysis of patients diagnosed between 2011 and 2016 in Hungary.
Authors: Krisztina Bogos, Zoltan Kiss, Lilla Tamási, Gyula Ostoros, Veronika Judit Dr Szabone Dr Muller, Nora Bittner, Veronika Sarosi, Aladar Vastag, ZSOFIA MARIA NAGY-ERDEI, Zoltan Polanyi, Andrea Daniel, Balazs Nagy, Krisztian Horvath, Zsolt Abonyi-Toth, Gyorgy Rokszin, Zoltan Voko, Judit Moldvay
Journal: Journal of Clinical Oncology (2020)

e21582 Background: Lung cancer is one of the most common cancers worldwide, however, 5-year survival is poor, only 10-20% of pataients survive this period. To date, no long-term study has been conducted to evaluate long-term survival rates in Hungary. Therefore, the objective of our study was to assess the 6-year survival of lung cancer patients (ICD-10 C34) based on a nationwide review of the National Health Insurance Fund (NHIF) database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between 1 January 2011 and 31 December 2016. Screening period was set for 2009-2010. Patients with other cancer-related ICD-10 codes 6 months before or 12 months after lung cancer diagnosis and those who received any anticancer treatment different from lung cancer protocols were excluded. Survival rates were evaluated according to year of diagnosis, patient gender and age, and morphology of lung cancer and main treatment type. Results: 41,854 newly diagnosed lung cancer patients were recorded. Mean age at diagnosis varied between 64.66 and 65.88 years during study period. One- and 5-year crude survival rates for the total population were 42.23% and 17.85%, respectively. Survival was significantly associated with gender, age and type of lung cancer based on statistical association. Female patients (n = 16,362) had 23% better survival (HR: 0.77 CI95% 0.75-0.79; p &lt; 0.001) than males (n = 25,492). The highest survival rates were found in the 20–49 age cohort (5Y = 31.3%) and if the cancer type was adenocarcinoma (5Y = 20.48%). We measured 5.3 % improvement in lung cancer survival between cases diagnosed in 2015-2016 vs. 2011-2012 (HR: 0.947 CI95% 0.92-0.97; p = 0.003). Survival of those lung cancer patients, whom had surgery in first line treatment without adjuvant therapy (3,120) reached 64.18%, those with adjuvant treatment (n = 2,675) 54.47% 5 year survival, while patients with chemotherapy (n = 11,780) had only 7.9% crude survival. Conclusions: Our study provided long-term LC survival data in Hungary for the first time. We found a 6% improvement in survival by the end of the study period in females and in the younger age groups. Survival rates were comparable to – and at the higher end of – rates registered in other East-Central European countries. Better survival rate of females could be attributed to a higher incidence rate of adenocarcinoma in women. Lung cancer patients diagnosed in early stage had 7-8 times better survival than those found in late stage.
Clinical significance of D-dimer in rapid screening for acute aortic dissection
Authors: 杨军, 王烁, 李春盛
Journal: BMJ (2010)

Objective To investigate clinical significance of D-dimer and other easily-obtained laboratory parameters in rapid screening for acute aortic dissection ( AAD). Methods Data of general health, clinical symptoms, white blood cell (WBC) count, serum levels of C-reactive protein (CRP),cardiac troponin Ⅰ (cTn Ⅰ ) and D-dimer in patients with confirmed AAD and acute coronary syndrome (ACS) were retrospectively analyzed. Significance of varied parameters in clinical diagnosis for AAD was evaluated by logistic regression model and their diagnostic values were evaluated by receiver operating characteristics (ROC) curve. Results Serum level of D-dimer increased significantly in patients with type Ⅰ AAD, as compared with that in those with type Ⅱ and type Ⅲ (P = 0. 111 and 0. 002, respectively). D-dimer, WBC and CRP all were independent risk factors for type Ⅰ AAD by logistic regression model fitted,with the largest effect of D-dimer. Analysis by ROC curve with sensitivities and specificities of serum levels of D-dimer and CRP, and WBC count also showed the same results. Conclusions Determination of serum level of D-dimer had significantly diagnostic value for AAD, and can be sued as rapid screening for it if combined with determinations of WBC and CRP.

Key words: 
Aortic diseases ;  Diagnosis ;  D-dimer ;
Abstract P114: Higher Pulse-oximetry Values are Associated with Greater Hemodynamics During Cpr And Success of Resuscitation
Authors: Giuseppe Ristagno, Shijie Sun, Max H Weil, Wanchun Tang
Journal: Circulation (2008)

Objectives. The use of peripheral pulse-oximetry during CPR has been controversial. We investigated peripheral oxygen saturation (SpO2) as an indicator of blood flow generated during CPR in a porci...
Results of a deep-dive survey on practice patterns of oncologists and advanced practice providers utilizing PARP inhibitors as maintenance therapy for patients with ovarian cancer.
Authors: Wendy Turell, Tariqa Ackbarali, Robert L. Coleman, Shannon Neville Westin, Judith Ann Smith
Journal: Journal of Clinical Oncology (2020)

e18044 Background: Often diagnosed at an advanced stage, most patients with ovarian cancer will relapse. As several PARP inhibitors (PARPi) have recently been approved as maintenance, patients are presented with treatment options that extend the interval of disease remission. However, novel challenges exist as oncology teams are apprehensive of integrating PARPi in practice. Emphasis on building this competence is essential for patients to obtain the maximum benefit of maintenance PARP therapy. Methods: Oncology teams were invited to participate in a 1-hour live and online education activity broadcast from 2018-2019 at OMedLive.com for 12 months. The activity addressed clinical data on the use of PARPi as maintenance therapy, management of adverse events, and emerging strategies utilizing PARP inhibition. A deep-dive survey, including structured and open-ended questions, was conducted 2 to 4 months after participation and focused on changes in practice, barriers to change, and observed patient outcomes. Results: In total, 915 clinicians participated in the video-based activity. Sixty physicians and advanced practitioners opted to complete the deep-dive survey, 70% of whom have used PARP inhibitors as maintenance therapy. Practice improvements were reported for identifying patients likely to benefit from PARPi (90%), differentiating among approved PARPi (86%), counseling patients (85%), and team-based side effect management (95%). The top 3 barriers to utilization of PARPi were lack of reimbursement (23%), inability to anticipate patient outcomes (15%), and unfamiliarity with clinical guidelines (15%). Variations in responses to open-ended questions included persistent questions (n = 47) in need of responses before adopting PARPi, data needed to better inform decision-making (n = 49), major concerns about PARPi (n = 55), and the most challenging aspects of current patient management with PARPi (n = 39). Conclusions: Patient education yielded improvements in practical application and management of PARP inhibitors for patients with ovarian cancer. The thematic variations in open-ended responses may inform the design of tailored interventions to improve clinical integration of PARP inhibitors as maintenance therapy and different lines of treatment.
Problems of diagnosis and treatment of neonatal hypoxic-ischemic encephalopathy
Authors: 封志纯
Journal: BMJ (2009)

缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)是新生儿常见疾病,发病率及致残率均高,故一直受到国际新生儿学界的高度重视[1-2].国外报道新生儿HIE的发病率为6‰,致死或致残率为1‰[3];国内报道新生儿HIE的发病率为9.2‰[4],与国外接近,但预后不良率明显高于国外,为9.42%～10.10%,尤其是重度HIE的预后不良率高达27%以[5-6],按照我国新生儿出生率2000万/年计算,则我国每年新出生的婴儿中可能有近200万为HIE患儿,其中20万可能预后不良.而加强对HIE的正确诊断与规范化治疗是改善其预后的关键.但是,目前国内HIE的诊断与治疗方面,不但在基层医院,而且在一些大型医疗单位,都不同程度地存在一些误区及诊断治疗欠规范的问题,应该引起重视。
<i>FOXO3</i> polymorphisms were correlated with gefitinib-induced hepatotoxicity in patients with non-small cell lung cancer.
Authors: Shaoxing Guan, Xi Chen, Min Huang, Li Zhang, Xueding Wang
Journal: Journal of Clinical Oncology (2020)

9578 Background: Drug-induced liver injury (DILI) is one of the most safety concern in drug development and clinical therapy. Severe hepatotoxicity of gefitinib often leads to acute/chronic liver injury, drug discontinuation and further treatment failure, however, the mechanism of gefitinib-induced hepatotoxicity remains unclear. AKT1/FOXO3 regulates expression of genes involved in multiple biological/pathological processes in liver cells, including apoptosis, oxidative stress, and cell-cycle transition, as well as expression of autophagy-related (Atg) genes. Therefore, we investigated the correlation between single nucleotide polymorphisms (SNP) in AKT1/ FOXO3 and gefitinib-induced hepatotoxicity in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 172 advanced NSCLC patients with activating EGFR mutations were enrolled and administered with gefitinib 250mg daily. 22 tag SNPs in AKT1/FOXO3 were selected by Heploview 4.2 and sequenced by Agena MassARRAY System. The associations between polymorphisms of AKT1/FOXO3 and gefitinib-induced hepatotoxicity were analyzed by Chi square test. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: FOXO3 rs4946935 and FOXO3 rs75544369 were found to be associated with gefitinib-induced hepatotoxicity in NSCLC patients. FOXO3 rs4946935 AA carriers have higher risk of developing gefitinib-induced hepatotoxicity than those with FOXO3 rs4946935 AG/GG. ( P = 0.018, OR = 12.414, 95%CI (1.53-100.711)). Patients with FOXO3 rs75544369 GA have higher risk of developing hepatotoxicity with P of 0.0002 (OR = 5.241, CI%(1.85-14.851)), or developing severe hepatotoxicity with P of 0.033 (OR = 2.963, 95%CI (1.090-8.059)), than those with FOXO3 rs75544369 GG. Conclusions: FOXO3 rs4946935 and FOXO3 rs75544369 are predictive biomarkers for gefitinib-induced hepatotoxicity in NSCLC patients. The mechanism underlying the association between FOXO3 polymorphisms and gefitinib-induced hepatotoxicity are worth investigating in further studies. Clinical trial information: NCT01994057 .
International retrospective cohort study of locoregional and systemic therapy in oligometastatic breast cancer (OLIGO-BC1).
Authors: Takayuki Ueno, XiWen Bi, Guangyu Liu, Sung Hoon Sim, Seock-Ah Im, Shintaro Takao, Kun Wang, Young-Hyuck Im, Manabu Futamura, Sung Gwe Ahn, Jeong Eon Lee, Yeon Hee Park, Masakazu Toi, Yasuhiro Fujiwara, Mari Saito-Oba, Yuko Kitagawa, Masahiko Nishiyama, Shigeru Imoto
Journal: Journal of Clinical Oncology (2020)

1025 Background: Systemic therapy is the standard care in metastatic breast cancer (BC). However, retrospective studies demonstrated survival benefits of locoregional and systemic (combination) therapy in oligometastatic BC. To clarify it, the Federation of Asian Clinical Oncology conducted an international retrospective cohort study (OLIGO-BC1) (UMIN No.000030047). Methods: Oligometastatic BC patients diagnosed from 2007 to 2012 were registered. “Oligometastases” is defined as low volume metastatic disease with limited number and size of metastatic lesions up to five and not necessarily in the same organ by the ABC guidelines. Overall survival (OS) from the diagnosis of oligometastases was the primary endpoint and compared between combination and systemic therapy using a log-rank test. Assuming the 5-year OS of 50% and 40%, respectively, 698 patients were required to achieve 80% power to detect the superiority of combination therapy, at a two-sided significance level. A multivariable Cox regression model with stratification by country was performed to estimate hazard ratio (HR) for therapy and other risk factors. Results: While 1,262 cases had been registered from February 2018 to May 2019, 1,200 remained for analysis after exclusion of unavailable cases. Among them, 573, 529 and 98 cases were registered from China, Japan and Korea, respectively. Luminal BC was recorded in 526 cases (44%), luminal-HER2 BC in 189 (16%), HER2 BC in 154 (13%), triple-negative BC in 166 (14%) and others in 165 (13%). One oligometastatic BC was found in 578 cases, 2 in 289, 3 in 154, 4 in 102 and 5 in 77. Bone metastases were recorded in 301 cases, visceral metastases in 387, locoregional recurrence in 25, local recurrence in 83 and multiple metastatic sites in 404. Combination therapy was performed in 595 cases and systemic therapy in 404. At median follow-up of 4.9 years, 5-year OS was 59.6% and 41.9%, respectively (p &lt; 0.01). An adjusted HR was 0.61 (95% CI: 0.51, 0.74). Type of systemic therapy, younger age, ECOG performance status 0, stage I BC, non-triple negative subtype, fewer metastatic sites, local recurrence and longer disease-free interval were significantly favorable prognostic factors. Discussions: Oligometastatic BC under some conditions seems to be curable. Taken together with recent molecular targeted therapy, locoregional therapy will be advantageous to conquer it. Conclusions: Combination therapy is a promising strategy for patients with oligometastatic BC.
巨细胞病毒感染致巨细胞肝炎一例临床病理分析
Authors: 周立, 于加海, 孙乃英, 郑国华
Journal: BMJ (2008)

患儿男,出生18 h,因出生后皮肤青紫,吃奶反应不佳伴吐沫,于2004年3月26日15:02入住我院新生儿科.患儿系G3P2L1足月顺产,生后窒息,Apgar评分6分.其母35岁,孕期健康,无不良嗜好及有害有毒物接触史。