tbuckley/cabot-search huggingface dataset:
Multiscale omic assessment of <i>EWSR1-NFATc2</i> fusion positive sarcomas to identify conserved fusion breakpoint and activation of the mTOR pathway.
Authors: Nathan David Seligson, Richard D Maradiaga, Colin W. Stets, Howard Katzenstein, Sherri Z. Millis, John L. Hays, James Lin Chen
Journal: Journal of Clinical Oncology (2020)

e23536 Background: EWSR1-NFATc2 ( E-N) fusion positive sarcomas are rare cancers historically categorized as Ewing sarcomas. Emerging evidence suggests unique molecular characteristics and chemotherapy sensitivities in these cancers. Here we present the largest cohort of genomically profiled E-N fusion positive sarcomas and evaluate their breakpoints and putative pathway alterations. Methods: Comprehensive genomic profiling of 1,024 EWSR1 fusion positive sarcomas, including 14 E-N fusions, was obtained through the Foundation Medicine research database (FMI). Additional data from the Gene Expression Omnibus, the Genomics of Drug Sensitivity in Cancer (GDSC), and The Cancer Genome Atlas (TCGA) datasets were used. Descriptive statistics, principle component analysis, differential expression, and pathway analysis were used as appropriate. Results: E-N fusions identified in the FMI database demonstrated consistent breakpoints located between exon 2 and 3 on NFATc2; consistent with previous reports suggesting that the primary transactivation domain and regulatory domains of NFATc2 are conserved in the EWRS1-NFATc2 fusion. Cluster analysis demonstrated separate E-N fusion positive sarcoma grouping than other EWRS1 sarcomas, while identifying an enrichment of mTOR pathway variants in E-N fusion positive samples (p = 0.05). Gene expression data from E-N identified a significant activation of the mTOR pathway in E-N positive sarcomas compared to either EWSR1-ETS (p = 0.002) or CIC-DUX4 positive sarcomas (p &lt; 0.001). In the GDSC database, NFATc2-High lines exhibited activation of the mTOR pathway (p &lt; 0.0001) and were more sensitive to the mTOR inhibitor rapamycin (p = 0.0006). Pan-cancer analysis of 33 non-overlapping TCGA datasets, elevated NFATc2 mRNA expression was significantly associated with activated RICTOR and mTOR signaling (p &lt; 0.0001). Elevated NFATc2 correlated with higher tumor grade and poorer progression-free survival and overall survival. Conclusions: Taken together, the data presented here suggests that E-N fusion positive sarcomas represent a distinct molecularly entity in comparison to traditional Ewing sarcomas. Conserved action of NFATc2 may correlate to mTOR over activation.
Relationship between pulmonary arterial hypertension and fibrinolysis in elder patients with chronic obstructive pulmonary disease
Authors: Li Han, Yi-hong Ding, Lin-zhi Xiao, Ying Zhang, Zheng-yan Chen, Qin Liu, Bin Xu
Journal: BMJ (2013)

A total of 40 patients with COPD (excluding those with correlated/relevant diseases) were measured for inflammation parameters of erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) after hospital admission and some coagulation/fibrinolysis parameters including D-dimer, thrombin-antithrombin (TAT), prothrombin fragment 1+ 2, (tissue plasminogen activator) tPA, plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (von WF), endothelin receptor A, thromboxane B2, P-selectin and pulmonary arterial pressure (PAP) by ultrasonic cardiography after the settling of the symptoms of acute period. All patients were then divided into 2 groups according to PAP [≤40 mm Hg (1 mm Hg=0.133 kPa) (n=24), >40 mm Hg (n=16)]. The values of CRP and ESR in the group with PAP>40 mm Hg were significantly higher than those in another group (P=0.044 and P=0.002 respectively) while tPA was lower (P=0.04). A moderate positive correlation existed between tPA and TXB2 (r=0.547). Moreover, a highly positive correlation was found between TXB2 and PAI-1 (r=0.929). The results indicated that the COPD patients with pulmonary arterial hypertension (PAH) tend to have a higher level of inflammation, and their fibrinolysis becomes impaired leading to a prothrombotic state.


Key words: 
Pulmonary disease, chronic obstructive; Hypertension, pulmonary
Prognostic role of T3/T4 ratio in metastatic renal cell carcinoma (mRCC): Preliminary results of the threeFOUR multicenter study (Meet-Uro 14).
Authors: Marco Maruzzo, Elena Verzoni, Francesco Pierantoni, Luca Galli, Francesca Vignani, Sebastiano Buti, Sandro Pignata, Elisa Zanardi, Andrea Sbrana, Giuseppe Procopio, Andrea Zivi, Teresa Zielli, Enrico Mini, Giandomenico Roviello, Umberto Basso, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2020)

e17093 Background: Thyroid hormones metabolism can be altered in patients (pts) with chronic diseases and/or undergoing cancer treatments. The prognostic role of T3/T4 ratio has been investigated in metastatic colorectal cancer pts in whom a high T3/T4 ratio predicted longer survival. No data are available in mRCC. Methods: We retrospectively reviewed the clinical charts of pts with mRCC treated in first line for metastatic disease at 8 Italian Oncology Units before March 2017, having at least one response assessment and baseline complete thyroid panel data available. T3/T4 was calculated as the ratio of the two value of hormones and categorized in tertiles. Results: We identified 96 pts, median age 62 years (range 27-82), 72% males. Sunitinib wad administered in 56% of pts, pazopanib in 38%, nivolumab and ipilimumab in 6%. According to Heng Score, 33% of the pts were at favorable risk, 58% at intermediate risk, 9% at poor risk. With a median follow-up time of 42.8 months, median PFS was 24.8 months, estimated median OS was 71.6 months. Tertile distribution of patients was 36.4% in the high, 29.1% in the medium and 34.5% in the low subgroup. A baseline high tertile value (≥ 0.35) predicted longer PFS (39.4 vs 21.8 1vs 4.5 months, p = 0.01), while median OS has not been reached in the three tertiles, with survival at 24 months being 69.7%, 82.1% and 91.4%, respectively in the low, medium, high group (p = ns). The high T3/T4 ratio is also strongly associated with the chance to achieve a partial or complete response (42.8% vs 39.9% vs 21%, X squared test, p &lt; 0.001). Heng prognostic model retained its prognostic role in this cohort (median OS was 77.1 vs 48.4 vs 22.3 months, p &lt; 0.001, respectively for favorable, intermediate or poor risk group) and also predicted PFS (median PFS 38.2 vs 17.2 vs 8.4 months, p = 0.004). Baseline NLR ≥ 3 predicted shorter OS (46.5 vs 77.1 months, p = 0.02) in the whole group. Conclusions: In our retrospective multicenter experience, a high T3/T4 ratio was associated with longer PFS and a higher probability to respond to the treatment. Median OS had not been reached for all the subgroups, probably due to a favorable patients selection. A longer follow-up is needed to validate the prognostic value of T3/T4 ratio in this cohort.
10-minute consultation Management of recurrent gout
Authors: 陈亮, 宋德香, 许国祥, 杨婧, 祝墡珠
Journal: BMJ (2008)

病史摘要患者,男性,84岁.主因突发左侧肢体无力伴肢体抽搐半天于2010年9月14日入院.患者于中午进餐时突然出现左侧肢体无力,言语不清,无头晕、头痛,无恶心、呕吐,继而出现四肢抽搐、意识障碍,无口吐白沫,无大小便失禁,持续约1 min后抽搐停止,神志转清,但仍有左侧肢体活动不利,外院行头颅CT检查示:右侧颞叶、顶叶梗死,脑萎缩,来我院就诊,以脑梗死、高血压病收入内科病房.自发病来患者精神可,二便正常,纳差,无明显消瘦史.既往高血压病史10余年,血压最高达180/120 mm Hg(1 mm Hg=0.133 kPa),目前服用氨氯地平治疗,血压控制不详.2年前有2次脑梗死病史,诊治具体不详,治疗后症状好转出院,平素未曾用药.否认其他慢性疾病史.个人史:吸烟史50余年,20支/d,否认饮酒史.家族史:否认家族性遗传疾病史。
Evaluation of a Program to Improve Linkage to and Retention in Care Among Refugees with Hepatitis B Virus Infection — Three U.S. Cities, 2006–2018
Authors: Janine Young, Colleen Payton, Patricia Walker, Daniel White, Megan Brandeland, Gayathri S. Kumar, Emily S. Jentes, Ann Settgast, Malini DeSilva
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Identification and management of hepatitis B infection in children and adults from countries with a high prevalence of infection, including refugees, is important for protecting their health and preventing transmission to others.
Concordance between CA-125 and RECIST progression (PD) in patients with germline BRCA-mutated platinum-sensitive, relapsed ovarian cancer treated with a PARP inhibitor (PARPi) as maintenance therapy after response to chemotherapy.
Authors: Angelina Tjokrowidjaja, Chee Khoon Lee, Michael Friedlander, Val Gebski, Laurence Gladieff, Jonathan A. Ledermann, Richard T. Penson, Amit M. Oza, Jacob Korach, Tomasz Huzarski, Luis Manso, Carmela Pisano, Rebecca Asher, Nicoletta Colombo, Tjoung-Won Park-Simon, Keiichi Fujiwara, Gabe S. Sonke, Ignace Vergote, Jae-Weon Kim, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2020)

6014 Background: There are no data to support CA-125 as a surrogate biomarker for ovarian cancer PD in patients on maintenance therapy with a PARPi. We aimed to assess the concordance of PD by CA-125 with RECIST PD in patients treated with maintenance PARPi. Methods: We extracted data on PD as defined by GCIG CA-125 and investigator-assessed RECIST from the SOLO2/ENGOT-Ov21 (NCT01874353) trial. Patients were categorized into: (i) CA-125 and RECIST non-PD concordant; (ii) CA-125 and RECIST PD concordant; and (iii) CA-125 and RECIST discordant. We excluded those with PD other than by RECIST, PD on date of randomization, and no repeat CA-125 beyond baseline. To assess the concordance of CA-125 PD with RECIST PD and CA-125 non-PD with RECIST non-PD, we computed the positive predictive value (PPV), i.e. the probability that patients with CA-125 PD also had RECIST PD, and negative predictive value (NPV), i.e. probability that patients with no CA-125 PD also did not have RECIST PD, respectively. Results: Of 295 randomised patients, 275 (184 olaparib, 91 placebo) were included in the primary analysis. 80 (29%) had CA-125 PD and 77 had concordant RECIST PD, resulting in a PPV of 96% (95% CI 90%-99%). Of 195 patients without CA-125 PD, 101 also did not have RECIST PD, resulting in a NPV of 52% (95% CI 45%-59%; Table). Among those with RECIST PD (n = 171), a greater proportion of patients with RECIST-only PD had a normal baseline CA-125 than those with both CA-125 and RECIST PD (94% vs 69%; p&lt; 0.001). Of 94 patients without CA-125 PD but had RECIST PD, 65 (69%) had CA-125 that remained within normal range, while 27 (29%) had rising and elevated CA-125 that did not meet the criteria for GCIG CA125-PD. Discordance between RECIST PD and CA-125 non-PD was similar in early (≤12 weeks) and late ( &gt; 12 weeks) PD (56% vs 55%, respectively; p= 0.96). Conclusions: Almost half the patients with RECIST PD did not have CA-125 PD and most had CA-125 still within the normal range. Regular imaging should be considered as part of surveillance in patients on maintenance olaparib rather than relying on CA-125 alone. [Table: see text]
新式剖宫产术后再次手术腹腔粘连情况分析
Authors: 陈惠梅, 李玉辉
Journal: BMJ (2007)

新式剖宫产术在我国开展至今已有10年,具有手术时间短、出血少、损伤少、术后恢复快,疼痛轻的优点,其最大的特点为不缝合腹膜.我院于1999年开展新式剖宫产术,取得了良好的效果.为了解新式剖宫产术后腹腔的粘连情况,论证新式剖宫产术不缝合腹膜的可行性,对316例再次行剖宫产术患者的资料进行回顾性分析,现将结果报道如下。
癫痫的正规治疗
Authors: 潘映辐
Journal: BMJ (2007)

癫痫是一种由多种病因引起的慢性脑部疾病,它的发作是由脑细胞反复发作的异常放电所引起.最常见的症状是抽风(惊厥),发作时突然神志不清(意识丧失)、全身发硬(强直)及(或)抽动;但也有不少癫痫患者发作时的症状不是惊厥,而表现为发愣、不动,或行为异常、情感异常、精神异常或自主神经功能紊乱的症状,这些症状可单独发生,也可以不同的组合发生。
口服拉莫三嗪致抗癫痫药高敏综合征一例
Authors: 杨勇, 沙悦, 黄程锦, 黄晓明
Journal: BMJ (2009)

患者女,19岁,因发热、皮疹2个月入院.患者于2008年3月15日因于院外诊为癫痫,服拉莫三嗪50 mg,2次/d.3月23日患者出现发热,体温最高37.8℃,当地医院予头孢曲松、地塞米松3 d未缓解,颊部出现针尖样红色丘疹、伴瘙痒,数天内向下波及前胸、后背及四肢,达手掌及足底,当地医院曾考虑为风疹、麻疹,相继予扑尔敏及病毒唑、阿昔洛韦等治疗,并将拉莫i嗪剂量减半,7 d后患者体温降至正常,皮疹略消退.4月6日患者自述服用原剂量拉莫三嗪后再次出现发热、皮疹,体温最高39℃.查血常规:白细胞14.7×109/L,分类中性粒细胞0.214,淋巴细胞0.67.肝功能:ALT 260 U/L,AST 138 U/L,乳酸脱氢酶(LDH)546 U/L.予病毒唑、头孢哌酮,停用拉莫三嗪,治疗无效.体温最高达40.3℃,皮疹加重,收入本院.既往体健.查体:体温36.7℃,全身皮肤可见直径约1～2 mm红色斑丘疹,压之可褪色,密集分布,部分融合成片,可见脱屑.左侧颌下、左颈部、双侧腹股沟可扪及多枚淋巴结,直径0.5～1.0 cm,质韧、可活动,无粘连、压痛,表面无破溃.张口受限,未见koplic斑.肝脾肋下未及。
Molecular correlates of response to preoperative olaparib alone or with cisplatin or with durvalumab in head and neck squamous cell carcinoma (HNSCC): A Hellenic Cooperative Oncology Group study.
Authors: Amanda Psyrri, George Papaxoinis, Niki Gavrielatou, Maria Gkotzamanidou, Panagiota Economopoulou, Ioannis Kotsantis, Aris Spathis, Maria Anastasiou, Stavros Gkolfinopoulos, Martha Nifora, George Fountzilas, Periklis Foukas
Journal: Journal of Clinical Oncology (2020)

6556 Background: Poly(ADP-ribose) polymerase (PARP) inhibitors drive increased DNA damage and tumor cell death, particularly in tumors with existing defects in DNA repair. Furthermore,they promote immune priming, through a range of molecular mechanisms. Foremost, among candidate intracellular pathways is STING (stimulator of interferon genes), an innate immune response activated by cytosolic DNA (perhaps a consequence of DNA damage) that can lead to enhanced interferon (IFN) production. PARP inhibitor-induced DNA damage also leads to adaptive upregulation of programmed death ligand 1 (PD-L1) expression. To this end, there is increasing rationale for testing PARP inhibitors alone or in combination with chemotherapy or PD1 checkpoint inhibitors in HNSCC. Methods: 39 patients were enrolled in OPHELIA phase II trial in which pts were randomized 3:3:3:1 to Cisplatin (C) 60 mg/m2 on d1 followed by Olaparib (O) 75mg d 1-5 (Arm A), O 300 mg bid for 21-28 days (Arm B), no treatment (ARM C) orD 1500 mg on d1 followed by O 600 mg daily for 21-28 days (Arm D). Response was defined as tumor reduction noted on exam, imaging or pathology. Pretreatment biopsies were subjected to 310 gene OncoDNA NGS panel. Double Stranded Brakes/Repair (DSB/R) was measured by evaluating phosphorylation of histone H2AX by immunochistochemistry (IHC). In addition, IHC for PD-L1 (CPS) and STING was performed in paired pre- and post-treatment biopsies. Results: 17/36 pts in (O) treatment arms (6/11 evaluable pts Arm A, 9/11 evaluable pts Arm B, 2/11evaluable\ pts arm D) developed a response. One patient in D+O arm developed path CR. Low γH2AX staining at pretreatment biopsies was associated with progression (p=0.029). Higher PD-L1 expression (CPS≥1) was associated with disease progression (p=0.014). CPS PD-L1 was upregulated following (O) treatment. STING expression was not significantly upregulated post treatment in (O) treatment arms. Alterations in genes that have been previously reported to be associated with (O) sensitivity, namely DNA damage Response/Repair (DDR) genes and genes involved in chromatin remodeling ( CHK2, KMT2D, KMT2C, ARID2 and AJUBA), were identified in responders. Conclusions: This window study demonstrated promising signs of activity of (O) in HNSCC, particularly in tumors with high expression of γH2AX and alterations in DDR or chromatin remodeling genes. Clinical trial information: NCT02882308 .
The change of serum C-reactive protein levels during molecular-targeted treatments could predict the response to anti-PD-1 treatment in metastatic renal cell carcinoma patients.
Authors: Kimiharu Takamatsu, Ryuichi Mizuno, Nozomi Hayakawa, Nobuyuki Tanaka, Takeo Kosaka, Eiji Kikuchi, Mototsugu Oya
Journal: Journal of Clinical Oncology (2020)

e17085 Background: Immuno-oncology (IO) checkpoint inhibitors, such as programmed death-1/programmed death-ligand1 (PD-1/PD-L1) inhibitors have been standard of care in the metastatic renal cell carcinoma (mRCC) systemic treatment. However, predictive biomarkers for IO checkpoint inhibitors which is clinically usable have been still unclear. The aim of this study was to evaluate the clinical significance of the change of serum C-reactive protein (CRP) levels during molecular-targeted treatments (VEGFR-TKI and mTOR-I) prior to nivolumab as the predictive marker for the response of nivolumab in patients with refractory mRCC. Methods: A total of 73 mRCC patients (favorable 25(34%), Intermediate 38(52%) and poor 10(14%) risk group by IMDC criteria) treated with nivolumab were retrospectively reviewed. We evaluated the serum CRP levels before and after molecular-targeted treatments. The elevation of serum CRP during molecular-targeted therapies before nivolumab induction was defined as the CRP-elevation group. The clinical impact of CRP-elevation as well as other clinical and pathological prognostic factors on progression-free survival (PFS) and overall survival (OS) from nivolumab were assessed. Results: The median follow-up period after nivolumab initiation was 13.2 months (range 3.0-60.8). Forty-nine patients (67%) were categorized into the CRP-elevation group. A clear impact of the CRP-elevation on the response of nivolumab was observed: the median PFS of the CRP-elevation group was 11.9 months, and that of the CRP-non elevation was not-reached (p = 0.038). On multivariate analysis, the CRP-elevation before nivolumab was the independent prognostic factor to predict PFS in nivolumab treatment (HR: 2.68, 95% CI: 1.01-7.11, p = 0.047). CRP-elevation group had a tendency of shorter OS than CRP-non elevation group (p = 0.071). Conclusions: The change of serum CRP levels during molecular-targeted therapies could be the predictive factor for the efficacy of nivolumab in mRCC patients.
Radiomic features for patients with primary soft tissue sarcomas: A prognostic study.
Authors: Sandro Pasquali, Marco Bologna, Gabriele Infante, Raffaella Vigorito, Antonella Messina, Carlo Morosi, Rosalba Miceli, Gabriella Greco, Alessandra Casale, Valentina Corino, Francesco Barretta, Luca Mainardi, Elena Palassini, Roberta Sanfilippo, Silvia Stacchiotti, Paolo Giovanni Casali, Dario Callegaro, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2020)

e23532 Background: Prognosis of extremity soft tissue sarcomas (ESTS) and retroperitoneal sarcomas (RPS) is currently estimated on clinical-pathological features, as those incorporated in the Sarculator nomogram. This study investigated the added value of end-point specific radiomic signatures (RS) in patients with primary ESTS and RPS. Methods: We retrospectively analysed data from patients with a ESTS (N = 100) or a RPS (N = 116) who underwent surgery (Jan2011-Dec2015) at one sarcoma reference institute and had magnetic resonance imaging (MRI) or computed tomography (CT) scan, respectively. Radiomic features were extracted from DICOM files of MRI and CT scan for ESTS and RPS, respectively. The study end-points were incidence of distant metastases (DM) and overall survival (OS) for ESTS and disease-free survival (DFS) and OS for RPS. A RS was established for each end-point. Models discriminative ability was measured using the Harrell c-index (C). Results: ESTS histology was undifferentiated pleomorphic sarcoma, myxofibrosarcoma, myxoid liposarcoma, dedifferentiated/pleomorphic liposarcoma, and others in 28, 21, 18, 9, and 24 patients, respectively. At a median follow-up of 61 months, the 5-yr DM-free rate and OS were 73.6% (95%CI 64.2-82.2%) and 73.4% (95%CI 64.5-83.6), respectively. A prognostic model based on the Sarculator and a DM-RS achieved higher C (0.86, 95%CI 0.77-0.93) than the Sarculator alone (0.83, 95%CI 0.71-0.94). For OS, the RS was not able to increase the Sarculator discriminative ability (Sarculator and OS-RS: C = 0.73, 95%CI 0.62-0.82; Sarculator alone: C = 0.72, 95%CI 0.62-0.81). RPS histology was well differentiated liposarcoma, dedifferentiated liposarcoma, leiomyosarcoma, and other in 22 (19%), 60 (52%), 22 (19%), and 12 (10%) patients, respectively. At a median follow-up of 58 months, 5-yr DFS and OS were 46.7% (95%CI, 37.8-57.6%) and 68% (95% CI 59.9-79.0%), respectively. RS extracted from CT scan without contrast enhancement slightly improve the discriminative ability of the Sarculator for DFS (Sarculator and DFS-RS: C = 0.65, 95%CI 0.57-0-72; Sarculator alone: C = 0.63, 95%CI 0.55-0.70) but not for OS (0.70, 95%CI 0.60-0.80 and 0.69, 95%CI 0.59-0.79, respectively). Conclusions: RS did not improve the discriminative ability of the Sarculator for OS. The added value for RS in relapse prediction (DM incidence for ESTS and DFS for RPS) deserves further investigations.
Final results of the multicenter, open-label, randomized phase II trial PAZOTHYR evaluating continuous versus intermittent administration of pazopanib in radio-iodine-refractory thyroid cancers (NCT01813136).
Authors: Christelle De La Fouchardiere, Yann Godbert, Cécile Dalban, Christine Do Cao, Frederic Illouz, Slimane Zerdoud, Johanna Wassermann, Stephane Bardet, Patrice Rodien, Cecile N Chougnet, Danielle Benisvy, Patricia Niccoli, Alain Ravaud, William Lebosse, Valérie Bourne-Branchu, Julien Gautier, Sophie Leboulleux
Journal: Journal of Clinical Oncology (2020)

6540 Background: Multikinase inhibitors (MKI) targeting angiogenesis, including pazopanib (P), have shown efficacy in progressive radioiodine refractory thyroid cancers (RAIR-TC) but are accompanied by adverse effects, leading to dose adjustments/interruptions. We aimed to investigate the efficacy and tolerance of a discontinuous scheme of pazopanib administration in this situation. Methods: This randomized phase II study enrolled RAIR-TC patients (pts) in first or second-line of MKI with documented disease progression within 12 months (m). After a 6-m pazopanib continuous induction phase, pts with stable disease (SD) or tumor response were randomly assigned in a 1:1 ratio to receive continuous pazopanib (CP) or intermittent pazopanib (IP) until progression and restart. They were stratified by best tumor response [stable disease vs. objective response] and prior MKI treatment [yes vs. no]). Primary endpoint was time to treatment failure (TTF) defined as time between randomization and permanent discontinuation of pazopanib (either for disease progression or intolerance); secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and safety. Results: 168 pts (66.5 years median age; 51.8% female) were included and 100 pts randomized (CP: 50, IP: 50). The median number of metastatic sites was 2.0 (1-7) and 50 pts (29.8%) were pretreated with MKI. With a median follow-up of 31.3 m, we did not show any statistically significant difference in the TTF, 80% (66.0-88.7%)] of the pts being under P at 6 m after randomization in the IP arm versus 78% (63.8-87.2%) in the CP arm. Median TTF was 14.7 m 95% CI [9.3; 17.4] and 11.9 m 95% CI [7.5; 15.6] respectively (HR 0.79 [0.49-1.27]). The best response with P was 35.6% (95% CI [28.2; 43.6]) and the disease control rate was 89.4% 95% CI [83.5; 93.7]. Median time to progression under P was not statistically different between 2 arms (5.7m 95% CI [4.8;7.8] in the IP arm vs. 9.2m 95% CI [7.3;11.1] in the CP arm (HR 1.36 [0.88; 2.12]). 36/100 pts (36%) experienced pazopanib-related grade 3/4 AEs (CP:17; IP: 19) mainly represented by gastrointestinal disorders, hypertension, cardiac disorders and asthenia. Five pazopanib-related deaths were reported (CP:1;IP: 4). Conclusions: The intermittent administration of pazopanib study did not significantly demonstrate superiority in efficacy or tolerance over continuous treatment. Continuous administration of MKI remains the standard in RAIR-TC. Clinical trial information: NCT01813136 .