tbuckley/cabot-search huggingface dataset:
Body Dysmorphic Disorder in Patients With Autism Spectrum Disorder: A Reflection of Increased Local Processing and Self-Focus
Authors: Sara B. Vasudeva, Eric Hollander
Journal: American Journal of Psychiatry (2017)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and in-teraction in addition to restricted, repetitive patterns of behaviors or interests.There is a substantial comorbidity with other psychiatric conditions, including social anxiety disorder, obsessivecompulsive disorder (OCD), affective disorders, and others (1).Case 1 "Mr.D" is a 25-year-old single white man who meets DSM-5 criteria for autism spectrum disorder (ASD), along with comorbid attention deficit hyperactivity disorder and a nonverbal learning disability (verbal IQ score, 99; performance IQ score, 79).He was diagnosed with ASD as a child and received early intervention and sensory integration services.He currently lives with his mother, is a college graduate, and is employed part-time.He has been preoccupied with the size, shape, coarseness, and color of his body hair, including hair on his wrists, abdomen, fingers, and eyebrows, for the past decade.He is compelled to monitor the hair's movement and position and whether or not hairs "stand out" and become observable to others, and this nearly constant preoccupation with body hair and compulsion to check his appearance in the mirror is distracting at work.He reports discomfort with any deviation from his expectations.He describes a heightened sensory sensitivity to movement of his hair and disorganization of the hair pattern, wanting it to be in a certain direction and "just so."For example, wind blowing his body hair causes a feeling of discomfort.This is associated with a high level of anxiety and feelings of shame and self-consciousness.In an attempt to reduce the anxiety and discomfort, he engages in compulsive grooming behaviors, finding the right way for hairs to sit on each finger, sometimes strategically pulling out hairs for a better overall look.On one occasion, he attempted to impose organization on his eyebrows with selective plucking, but he was not satisfied with the result.He admits that it is "ridiculous," but the discomfort feels "real."The compulsions are time-consuming and interfere with his performance of tasks at work, and as a result he has repeatedly been fired from jobs.
Free light chain assay and cytogenetic abnormalities for identification of high-risk smoldering myeloma.
Authors: Jeremy Todd Larsen, Shaji Kumar, Wilson I. Gonsalves, Vinay Gupta, Brandt L. Esplin, Rhett P. Ketterling, William Morice, Robert A. Kyle, Angela Dispenzieri, S. Vincent Rajkumar
Journal: Journal of Clinical Oncology (2014)

8595 Background: Translocation (4;14) and deletion 17p in smoldering multiple myeloma (SMM) have been identified as high risk cytogenetic abnormalities (CAs). Risk stratification incorporating CAs and biomarkers are needed to identify high risk SMM patients. The aim of this study was to determine the predictive value of the free light chain (FLC) assay in combination with high-risk CAs. Methods: The study included SMM patients seen at Mayo Clinic from 1991-2010 screened for available FISH and serum FLCs at diagnosis. Receiver operating characteristics analysis determined the optimal involved FLC (iFLC) cut-point to predict progression to MM within 24 months. Univariate analysis and multivariate analysis were performed. Time to progression (TTP) was calculated using Kaplan-Meier analysis. Results: The FLC was measured in 249 patients; t(4;14) was found in 33 (13.3%) and deletion 17p in 6 (2.4%). Median age at SMM diagnosis was 62 years (range, 30-90). The optimal iFLC cut-point was 41 mg/dL. The iFLC was >40 in 23% of the 39 high-risk CA (n=9) and 22% of non-high risk CA patients (n=46). In the high-risk CAs group, median TTP if iFLC >40 was 20 months (95% CI 5-24) versus 30 months (19-60) in the iFLC <40 group. In the low-risk CAs, median TTP if iFLC >40 was 34 months (26-51) versus 62 months (48-86) in the iFLC <40 group (p <0.0001). One and two-year progression rates for iFLC >40 in high-risk CAs were 23% and 89%. In comparison, progression rates were 7% and 14% at one and two years in low-risk CAs with iFLC <40. Table 1 shows the univariate and multivariate analysis. Conclusions: Integration of the FLC assay and CAs may facilitate recognition of SMM patients at highest risk for rapid progression as increasing hazard with each risk factor was demonstrated . Elevation of the iFLC >40 in the presence of adverse CAs identified a high-risk subset with 90% progression at 24 months for whom early intervention strategies may be considered. Variable Univariate Multivariate HR 95% CI P HR 95% CI P iFLC >40 1.9 1.3-2.8 0.0007* 1.8 1.2-2.5 0.004* Age >65 1.8 1.3-2.4 0.001* 1.6 1.1-2.2 0.007* BMPC % >20 2.0 1.4-2.7 0.0001* 1.7 1.3-2.4 0.0007* M-spike >3 1.3 0.89-1.8 0.19 β-2 microglobulin >3.5 1.7 0.72-3.8 0.21 Albumin <3.5 1.1 0.44-2.5 0.80
SORAVE: Phase I study for the treatment of relapsed solid tumors with the combination of sorafenib and everolimus.
Authors: Lucia Nogova, Christian Mattonet, Matthias Scheffler, Marc Christiaan Allardt Bos, Masyar Gardizi, Irini Papachristou, Noemi Muthen, Denis Rokitta, Martina Kinzig, Fritz Soergel, Uwe Fuhr, Deniz Kahraman, Carsten Kobe, Kerstin Rhiem, Peter Mallmann, Roland Schnell, Ildiko Katay, Max Schlaak, Markus Dietlein, Juergen Wolf
Journal: Journal of Clinical Oncology (2012)

3044 Background: Dual inhibition of signaling pathways interfering with angiogenesis and cell proliferation may increase anti-tumor efficacy. We evaluated the combination of the VEGFR inhibitor sorafenib (S) and the mTOR inhibitor everolimus (E) and used FDG-PET to assess pharmacodynamic (PD) activity of E. Methods: Patients with relapsed solid tumors were treated with escalating doses of E 2.5-10.0mg/d p.o. in a 14 days monotherapy run in phase followed by combination therapy with a fixed dose of S 400mg bid from day 15. The primary aim was to define a safe and feasible combination treatment regimen for a subsequent phase II trial. DLT was defined as any drug related toxicity of CTC IV° or toxicity requiring hospitalization or interruption of therapy for more than 2 weeks within the first 29 days of treatment. Pharmacokinetic (PK) analyses were performed on day 5, 14 and 29 combined with explorative PD assessment of E by FDG-PET on days 1, 5 and 14 of treatment. Results: Nineteen patients were treated with the combination of E and S. The DLT was not reached according to protocol definition. However, at a dose level of E 10mg/d p.o. the following adverse events (AE) occurred in the non-DLT interval: Pneumonia III°, treatment delay due to leucopoenia/thrombopenia III° and sudden cardiac death probably due to arrhythmia. Based on these observations, the dose level of 7.5mg/day E p.o. in combination with 400mg S bid was defined as the MTD. The steady state of E alone was reached after 5 days of treatment and did not change until day 14. However, on day 29 everolimus plasma concentrations (AUC and Cmax) showed a significant 30 % reduction when co-administered with S. A metabolic response of the hottest lesion in PET on day 5 defined as ≤ 80% of baseline was seen in 4 of 15 evaluable patients. Median PFS and OS were 4.2 and 5.4 months, respectively. A patient with neuroendocrine carcinoma reached the longest PFS of 16.6 months. Conclusions: Treatment of patients with relapsed solid tumors with a combination of E 7.5mg/day and 400mg S bid is safe and feasible. The extension phase for confirmation of safety data, further PK and PD modeling and preliminary exploration of efficacy in KRAS mutant cancer patients will be performed at this dose level.
O-mel-sora: A national multicenter phase II trial of sorafenib in metastatic uveal melanoma.
Authors: Frédéric Mouriaux, Vincent Servois, Sophie Piperno-Neumann, Thierry Lesimple, Antoine Thyss, Thomas Jouary, Eve-Marie Neidhardt, Nicolas Penel, Corinne Delcambre, Jean-Jacques Parienti, Caroline Serre-Henry, Florence Joly
Journal: Journal of Clinical Oncology (2014)

e20004 Background: Uveal melanoma is the most common primary ocular malignancy in adults, accounting for 70 % of all eye malignancy. Despite adequate local treatment, about 30-50 % of patients develop metastasis and the survival rate is 50% after 10 years and the median survival time is 5-7 months after development of metastasis. There is no consensual and effective treatment in metastatic uveal melanoma. Preclinical data suggest that sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis may be a potential treatment of metastatic uveal melanoma (IC50 values of sorafenib to inhibit cell proliferation was 2.9 µM, similar in both V599EBRaf and WTBRaf melanoma cells). Methods: Multicenter, non-comparative, non-randomized, phase II study was conducted. The primary objective was to determine the non-progression rate at 6 months for patients receiving Sorafenib at dose of 400 mg twice per day orally according the RECIST criteria. Results: 32 patients were enrolled in this study and 29 patients were evaluable. Non-progression at 6 months was observed in 11 patients (38%). Non-progression at 12 months was observed in 4 patients (13%). The overall survival was 10 months. Conclusions: Sorafenib at dose of 400 mg twice per day orally showed limited potential clinical benefits in patients with metastastic uveal melanoma. Clinical trial information: 2010-022527-29.
Localized prostate cancer and salvage treatment: EBRT first + salvage HIFU or HIFU first + salvage EBRT? A single-institution matched pair analysis over a 20-year period.
Authors: Gilles Pasticier, Ji-Wann Lee, Sebastien Crouzet, J Soria, Christelle Medollima, Florence Mege-Lechevallier, Jean-Yves Chapelon, Olivier Rouviere, Albert Gelet
Journal: Journal of Clinical Oncology (2017)

77 Background: In the field of curative treatment for localized prostate cancer, HIFU (High Intensity Focused ultrasound) is one of salvage option after EBRT(external beam radiation therapy) failure and EBRT is the standard salvage option for local relapse after HIFU.Our aim was to compare and evaluate the oncologic outcomes between HIFU first + salvage EBRT versus EBRT first +salvage HIFU. Methods: Using a matched pair analysis, 342 Patients (171 in each group) treated between 1994 and 2014 in the same institution were prospectively followed and matched to a 1:1 basis. Outcome measurements: Overall Survival Rate(OSR), cancer specific(CSSR) and metastasis free (MFSR) survival rates were the primary endpoints. Secondary endpoints were survival rate free of hormone therapy (HTFR) and the rate of side effects Clavien score ≥ 3. Results: Mean follow-up were 114 and 124 months for HIFU+ S-EBRT and EBRT + S-HIFU respectively. At 7 years from the primary treatment , the MFSR were significantly better after HIFU first +S- EBRT than after EBRT first+S- HIFU: 96% vs 91%% (p:0.011). The OSR and the CSSR were not significantly different in the two arms (97% and 99% after HIFU+S- EBRT versus 96% and 98% after EBRT+S- HIFU). The HTFR at 7 years was significantly different (p &lt;0.001) after HIFU+ S-EBRT than after EBRT+ S-HIFU 90% versus 69%. In multivariable Cox regression, the initial Gleason sum ≥ 8 and the treatment strategy were predictors of MFSR (risk ratio 3.2 for treatment modality). The rate of side effect Clavien score≥ 3 was significantly higher (p:0.01) in the EBRT+ S-HIFU arm than in the HIFU+ S-EBRT arm. The rate of urinary toxicity (severe incontinence and bladder outlet obstruction) were worse in the EBRT+ S-HIFU arm than in HIFU+S-EBRT arm: 9.4% and 15.2% vs 1.2% and 7.6% (p:0.01 and 0.078). Conclusions: In this single-institution Matched Pair comparison, the MFSR and HTFR were significantly better in the HIFU+S-EBRT arm than in the EBRT+S-HIFU arm. The rate of urinairy toxicity and Clavien≥3 side-effects were Higher in the EBRT + S-HIFU arm than in the HIFU + S-EBRT arm.
Quadrivalent HPV Vaccination and the Risk of Adverse Pregnancy Outcomes
Authors: Nikolai M. Scheller, Björn Pasternak, Ditte Mølgaard-Nielsen, Henrik Svanström, Anders Hviid
Journal: New England Journal of Medicine (2017)

The quadrivalent human papillomavirus (HPV) vaccine is recommended for all girls and women 9 to 26 years of age. Some women will have inadvertent exposure to vaccination during early pregnancy, but few data exist regarding the safety of the quadrivalent HPV vaccine in this context.We assessed a cohort that included all the women in Denmark who had a pregnancy ending between October 1, 2006, and November 30, 2013. Using nationwide registers, we linked information on vaccination, adverse pregnancy outcomes, and potential confounders among women in the cohort. Women who had vaccine exposure during the prespecified time windows were matched for propensity score in a 1:4 ratio with women who did not have vaccine exposure during the same time windows. Outcomes included spontaneous abortion, stillbirth, major birth defect, small size for gestational age, low birth weight, and preterm birth.In matched analyses, exposure to the quadrivalent HPV vaccine was not associated with significantly higher risks than no exposure for major birth defect (65 cases among 1665 exposed pregnancies and 220 cases among 6660 unexposed pregnancies; prevalence odds ratio, 1.19; 95% confidence interval [CI], 0.90 to 1.58), spontaneous abortion (20 cases among 463 exposed pregnancies and 131 cases among 1852 unexposed pregnancies; hazard ratio, 0.71; 95% CI, 0.45 to 1.14), preterm birth (116 cases among 1774 exposed pregnancies and 407 cases among 7096 unexposed pregnancies; prevalence odds ratio, 1.15; 95% CI, 0.93 to 1.42), low birth weight (76 cases among 1768 exposed pregnancies and 277 cases among 7072 unexposed pregnancies; prevalence odds ratio, 1.10; 95% CI, 0.85 to 1.43), small size for gestational age (171 cases among 1768 exposed pregnancies and 783 cases among 7072 unexposed pregnancies; prevalence odds ratio, 0.86; 95% CI, 0.72 to 1.02), or stillbirth (2 cases among 501 exposed pregnancies and 4 cases among 2004 unexposed pregnancies; hazard ratio, 2.43; 95% CI, 0.45 to 13.21).Quadrivalent HPV vaccination during pregnancy was not associated with a significantly higher risk of adverse pregnancy outcomes than no such exposure. (Funded by the Novo Nordisk Foundation and the Danish Medical Research Council.).
Intratumoral heterogeneity of ERBB2/HER2 expression in micropapillary urothelial carcinoma.
Authors: Sumit Isharwal, Hongying Huang, Gouri Nanjangud, Francois Audenet, Yingbei Chen, Anuradha Gopalan, Samson Fine, Satish Tickoo, Gopa Iyer, Jonathan E. Rosenberg, Dean F. Bajorin, Harry W. Herr, S. Machele Donat, Guido Dalbagni, Bernard H. Bochner, David B. Solit, Victor E. Reuter, Hikmat Al-Ahmadie
Journal: Journal of Clinical Oncology (2017)

383 Background: Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. Histologically, most of these tumors are associated with variable amounts of “not otherwise specified (NOS)” urothelial carcinoma. MPUC has been shown to be associated with ERBB2/HER2 amplification and protein overexpression. However, the status and distribution of these findings within the different components of tumors containing both MP and NOS urothelial carcinoma have not been addressed. Methods: We identified 44 cases of MPUC that had tissue available for FISH and IHC at our institute, of which an NOS component sufficient for both FISH and IHC was identified in 37 cases. We followed the updated ASCO/CAP Guidelines for breast cancer and as such amplification was defined by a HER2/CEP17 ratio of ≥ 2.0 or &gt; 6 copies of the gene and HER2 overexpression was considered with IHC scores of 2+ and 3+. Results: In urothelial tumors with both MP and NOS components (n = 37), ERBB2 amplification in MP and NOS components was present in 25 and 16 cases respectively. ERBB2 amplification was significantly higher in the MP component compared to NOS component within the same tumor (67.57% vs. 43.24%, p = 0.049). HER2 overexpression in MP and NOS components was present in 25 and 13 cases respectively. HER2 overexpression was significantly higher in the MP component compared to NOS component within the same tumor (67.56% vs. 35.13%, p = 0.012). In addition, ERBB2 amplification strongly correlated with HER2 overexpression in both MP (rho = 0.65, p &lt; 0.001) and NOS (rho = 0.74, p &lt; 0.001) components. In this cohort (n = 44), tumor stage and lymph node status were significant predictors for overall survival (p = 0.01, &lt; 0.001 respectively). However, ERBB2 amplification and HER2 overexpression in MP component were not associated with patients’ survival outcome (p = 1.00, 0.75 respectively). Conclusions: In MPUC, ERBB2 amplification and HER2 overexpression were preferentially but not exclusively identified in MP component compared to NOS component within the same tumor. Our findings provide evidence for intratumoral heterogeneity of ERBB2 amplification and HER2 expression in MPUC.
Prognostic factors in patients (pts) with advanced biliary tract cancer (BTC) treated with first-line gemcitabine plus cisplatin (GEMCIS): Retrospective analysis of 740 pts.
Authors: Hyungwoo Cho, Bumjun Kim, Changhoon Yoo, Kyu-Pyo Kim, Jaewon Hyung, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Jin-hong Park, Heung-Moon Chang, Baek-Yeol Ryoo
Journal: Journal of Clinical Oncology (2017)

424 Background: BTC is a heterogeneous group of disease consisted of intrahepatic, extrahepatic cholangiocarcinoma and gallbladder cancer. Although GEMCIS has been established as a standard first-line chemotherapy based on the ABC-02 trial, more data is needed to define the clinical course of BTC and its prognostic factors. Methods: Between April 2010 and May 2015, 740 pts with histologically documented BTC were treated with first-line GEMCIS in Asan Medical Center, Seoul, Korea. All pts received GEMCIS as described in the ABC-02 trial. Response was graded according to the RECIST version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Maier curves. Multivariate analyses were performed to define prognostic factors. Results: Median age was 60 years (range, 27-82) and 425 (57%) pts were male. Initially metastatic disease was the most common disease status at GEMCIS (n = 377, 51%) followed by recurrence after surgery (279, 38%) and locally advanced unresectable disease (84, 11%). Liver (37%) and peritoneum (25%) were the common metastatic sites. Pts received a median 5 cycles of GEMCIS (range, 1-42). Objective response rates were 13% and there was no significant difference according to the primary tumor sites (p = 0.45). With a median follow-up duration of 27.3 months (mo) (95% CI, 24.2-30.5), median PFS and OS were 5.2 mo (95% CI, 4.7-5.6) and 10.4 mo (95% CI, 9.6-11.2), respectively. In the multivariate analyses, male gender (female vs male; HR = 0.83), pretreatment CA 19-9 level (elevated vs normal; HR = 1.31), initially metastatic disease (vs locally advanced disease, HR = 1.92), poor performance status (ECOG 2 vs 0-1; HR = 1.45), and measurable disease by the RECIST criteria (vs non-measurable; HR = 1.40) were significantly associated with poorer OS (p &lt; 0.05 for all). Conclusions: Our retrospective analysis based on large number of pts demonstrated that first-line GEMCIS in the real world setting has comparable efficacy with the results of the ABC-02 trial. Prognostic factors demonstrated in this study may help to predict clinical outcomes and design future clinical trials for advanced BTC.
<i>SOX2</i> and <i>FGFR1</i> gene copy number in surgically resected non-small cell lung cancer (NSCLC).
Authors: Luca Toschi, Giovanna Finocchiaro, Teresa T. Nguyen, Margaret Skokan, Laura Giordano, Letizia Gianoncelli, Matteo Perrino, Licia Siracusano, Annarita Destro, Maurizio Infante, Marco Alloisio, Luigi Terracciano, Massimo Roncalli, Armando Santoro, Marileila Varella-Garcia
Journal: Journal of Clinical Oncology (2012)

7061 Background: SOX2 is a member of the SRY-related HMG-box family of transcription factors and has been shown to be frequently amplified and overexpressed in squamous cell lung cancer, with conflicting results regarding its prognostic relevance. Similarly, FGFR1, a transmembrane tyrosine kinase receptor belonging to the fibroblast growth factor receptor family, has been recently reported to be amplified in squamous cell lung carcinomas, suggesting a potential role for FGFR1 as a therapeutic target in NSCLC. Aim of the present study is to evaluate SOX2 and FGFR1 gene copy number in surgically resected NSCLCs, to investigate their prognostic relevance and their association with clinico-pathological characteristics. Methods: SOX2 and FGFR1 gene copy number was assessed by fluorescence in situ hybridization (FISH) in tissue microarray cores from 447 surgically resected NSCLCs. Each patient was given a score ranging from 1 to 6 according to increasing mean copy number per cell of each gene, with 6 indicating true gene amplification. Results: SOX2 and FGFR1 FISH was successfully performed in 445 patients (pts), which were grouped as + (score 5-6) and - (score 1-4). Using this scoring system 105 (23.6%) pts tested SOX2+, while 74 (16.6%) pts resulted FGFR1+. True gene amplification for SOX2 and FGFR1 was observed in 19 (4.3%) and 37 (8.3%) cases, respectively. SOX2+ and FGFR1+ status was significantly associated with squamous histology (p&lt;.001). Additionally, SOX2+ pts had a significantly higher chance of being former/current smokers, male and FGFR1+. FGFR1 gene status had no prognostic impact in the whole population and in the squamous cell carcinoma subgroup. Conversely, SOX2+ pts had significantly longer overall survival compared with SOX2- pts (HR 0.68, p=.020). When restricting survival analysis to squamous cell histology, stage I-II SOX2+ pts had a significant survival advantage compared with SOX2- group (HR 0.38, p=.006), while no difference was observed in stage III-IV pts. Conclusions: Increased SOX2 and FGFR1 gene copy number is a common event in lung cancer pts with squamous cell histology. SOX2 gene gain is a favorable prognostic factor in surgically resected pts, particularly in early stage squamous cell cancers.