tbuckley/cabot-search huggingface dataset:
Safety and efficacy of hydrogen peroxide topical solution, 40% (w/w), in patients with seborrheic keratoses: Results from 2 identical, randomized, double-blind, placebo-controlled, phase 3 studies (A-101-SEBK-301/302)
Authors: Leslie S. Baumann, Andrew Blauvelt, Zoe D. Draelos, Steven E. Kempers, Mary P. Lupo, Joel Schlessinger, Stacy R. Smith, David C. Wilson, Mark Bradshaw, Esther Estes, Stuart D. Shanler
Journal: Journal of the American Academy of Dermatology (2018)

<h3>Background</h3> Approved topical treatments for seborrheic keratoses (SKs) are an unmet need. <h3>Objective</h3> To evaluate the safety and efficacy of 40% hydrogen peroxide topical solution (HP40) versus vehicle for the treatment of SKs (A-101-SEBK). <h3>Methods</h3> A total of 937 patients with 4 SKs each (≥1 lesion each on the face and on the trunk and/or an extremity) were randomized 1:1 to HP40 or vehicle. At each visit, SKs were graded using the Physician's Lesion Assessment (PLA) scale (0, clear; 1, nearly clear; 2, ≤1 mm thick; and 3, >1 mm thick). After 1 treatment, SKs with a PLA score higher than 0 were re-treated 3 weeks later. <h3>Results</h3> At day 106, significantly more patients treated with HP40 than with vehicle achieved a PLA score of 0 on all 4 SKs (study 1, 4% vs 0%; study 2, 8% vs 0% [both <i>P</i> < .01]) and on 3 of 4 SKs (study 1, 13% vs 0%; study 2, 23% vs 0% [both <i>P</i> < .0001]). A higher mean per-patient percentage of SKs were clear (study 1, 25% vs 2%; study 2, 34% vs 1%) and clear or nearly clear (study 1, 47% vs 10%; study 2, 54% vs 5%) with HP40 than with vehicle. Local skin reactions were largely mild and resolved by day 106. <h3>Limitations</h3> The optimal number of treatment sessions was not evaluated. <h3>Conclusion</h3> Application of HP40 was well tolerated and effective in the removal of SKs.
VIOLETTE: A randomized phase II study to assess DNA damage response inhibitors in combination with olaparib (Ola) vs Ola monotherapy in patients (pts) with metastatic, triple-negative breast cancer (TNBC) stratified by alterations in homologous recombination repair (HRR)-related genes.
Authors: Andrew Tutt, Christine Stephens, Paul Frewer, Andrew Pierce, Joon Rhee, Karen So, Lone Ottesen, Emma Dean, Simon J. Hollingsworth
Journal: Journal of Clinical Oncology (2018)

TPS1116 Background: Invasive BC is diagnosed in > 255,000 pts in the US annually, and TNBC comprises ≈15% of cases. Alterations in BRCA1/2 are associated with ≈5% of all BCs. Ola (a poly ADP-ribose polymerase inhibitor [PARPi]) is approved in the US for treating pts with HER2-negative metastatic BC with germline BRCA mutation (gBRCAm). Pts treated with Ola had significant and clinically meaningful improvements in progression-free survival (PFS) vs pts treated with "physician's choice" of chemotherapy. Similarly, alterations in other non-BRCA1/2 HRR genes (non-BRCA HRRm) may confer sensitivity to Ola therapy in pts with TNBC. Ola, AZD1775 (a WEE1 checkpoint inhibitor) and AZD6738 (an ataxia telangiectasia and Rad3-related protein inhibitor) target DNA damage repair and cell cycle regulation. Both Ola + AZD1775 and Ola + AZD6738 had synergistic antitumor effects vs Ola monotherapy in preclinical studies, supporting the clinical evaluation of these combinations vs Ola monotherapy in pts with TNBC. Methods: In this global, multicenter, open-label, phase II study (NCT03330847), 450 pts with advanced TNBC will be randomized (1:1:1) to 3 treatment arms 1) Ola 200 mg bid + AZD1775 175 mg bid, 2) Ola 300 mg bid + AZD6738 160 mg qd, or 3) Ola 300 mg bid. All pts will undergo centralized tumor molecular testing to detect mutation(s) in 15 HRR genes and ≈150 pts will be assigned to each of the 3 biomarker strata (A: BRCAm; B: non-BRCA HRRm; C: non-HRRm). All pts will be stratified by prior platinum exposure. Eligible pts will have received ≤2 prior lines of chemotherapy for metastatic disease, including an anthracycline or taxane. Exclusion criteria include prior PARPi therapy. The primary endpoint is PFS (each combination vs Ola alone) analyzed by blinded, independent central review (RECIST v1.1). Secondary endpoints are objective response rate, duration of response, change in tumor size, and overall survival for comparisons between combinations and for each combination vs Ola alone; drug exposure; and safety and tolerability. Enrollment is ongoing. Clinical trial information: NCT03330847.
Dual targeting of EGFR and HER3 with cetuximab and MM-121/SAR256212 in HNSCC patient derived xenograft (PDX) models.
Authors: Nabil F. Saba, Dongsheng Wang, Guoquing Qian, Hongzheng Zhang, Mihir Patel, Mark El-Deiry, J. Trad Wadsworth, Kelly R. Magliocca, Sreevinas Nannapaneni, Dong Moon Shin, Fadlo Raja Khuri, Zhuo Georgia Chen
Journal: Journal of Clinical Oncology (2015)

e17066 Background: The epidermal growth factor receptor (EGFR) family member-3 (HER3) signaling plays an important role in resistance to (EGFR)-targeted therapy in head and neck squamous cell carcinoma (HNSCC). To better understand the effect of combining an anti-HER3 antibody MM-121/SAR256212 with cetuximab in HNSCC, we studied this drug combination utilizing patient derived xenograft (PDX) models of HNSCC. Methods: Cetuximab resistant HNSCC cell line SCC1-C and its parental cell line SCC1-P were treated with cetuximab, MM121 and their combination. HER3 activation, AKT and ERK signaling pathways were evaluated by western blotting. SRB and colony formation assays were performed to investigate the combined effect of MM121 and cetuximab on cancer cell growth. SCC1-C xenograft and PDX models were carried out to evaluate the efficacy of MM121 and cetuximab combination. Results: Cetuximab induced HER3 activation in cell lines; the combined treatment blocked EGFR and HER3 and inhibited PI3K/AKT and ERK as well as cell growth more effectively compared to each of the antibodies in vitro. Both cetuximab resistant HNSCC xenograft and the PDX models revealed a better efficacy of the combination compared to the single antibodies. In PDX models from patients A(T4aN2c floor of mouth), C(T4aN2b pyriform sinus), and D(T4bN2b retromolar trigone), both cetuximab and the combination inhibited tumor growth (p < 0.001 for both treatments). There was no significant difference between cetuximab and the combination in tumors A and C, but in D, the combination was significantly more effective (p < 0.001). After discontinuation tumors treated with cetuximab recurred in patient A’s PDX, whereas relapse was undetectable in the combination. In patient B’s PDX (T4aN2b of the alveolar ridge), only the combination inhibited tumor growth (p = 0.004) and was more effective than cetuximab (p = 0.032). Conclusions: Dual targeting with of cetuximab and MM-121 was more effective than cetuximab alone in a HNSCC PDX model. Since this model is highly clinically predictive, it provides a compelling rationale for further clinical investigation of this combination in patients with HNSCC who have progressed following cetuximab therapy.
The $2.5 Million Wage Gap in Cardiology
Authors: Rashmee U. Shah
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Changes to sharing medical records could damage research, report warns
Authors: Nigel Hawkes
Journal: BMJ (2018)

From 25 May patients in the UK have a simpler way of choosing not to share their patient records, a change that could damage health related research, a report from the King’s Fund warns.1

The change has been introduced at the same time as the General Data Protection Regulation, which has been discussed widely as organisations email people on their lists to seek their permission to continue doing so.

But the change to the NHS opt-out has been less widely publicised, and no special effort has been made to convince patients that their data will be safe and that using the data could improve care and the way the NHS is run.

The …
Core Outcome Sets for Psoriasis Clinical Trials
Authors: Bruce E. Strober, Kenneth B. Gordon
Journal: JAMA Dermatology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
OWE-002 Significance of biopsies before large colorectal endoscopic resections and histopathological features of high risk lesions
Authors: Andrew Emmanuel, Shraddha Gulati, Monica Ortenzi, Margaret Burt, Bu Hayee, Amyn Haji, Salvador Diaz-Cano
Journal: Endoscopy (2018)

<h3>Introduction</h3> Guidelines on endoscopic resection (ER) of colorectal superficial neoplastic lesions (CSNL) recommend against biopsy sampling but many are extensively sampled prior to referral, despite the deleterious effect on ER, to exclude adenocarcinoma or high grade dysplasia (HGD), reflecting a lack of understanding of the incidence and nature of adenocarcinoma or HGD within different morphological sub-types. It is therefore important to define the significance of HGD on biopsy samples and place this in the context of the histopathological characteristics of high risk lesions. <h3>Methods</h3> ERs of large (≥2 cm) CSNL were included. Sensitivity and specificity of HGD on biopsy and higher risk morphology (laterally spreading tumour (LST) non-granular/LST mixed nodular type/IIc component) for diagnosing covert invasive adenocarcinoma and confirmed HGD after ER were calculated and compared (Mcnemar's test). In addition, 50 high risk lesions (containing HGD or invasive adenocarcinoma) were subjected to more detailed histopathological analysis. <h3>Results</h3> Results from prior biopsy sampling were available for 291 lesions (mean size 62.8 mm). Histopathology after ER revealed HGD in 85 (29%) and invasive adenocarcinoma in 26 (9%). Sensitivity and specificity of HGD on biopsy (n=60) for invasive adenocarcinoma were 50% (95% CI 32%–68%) and 82% (95%–CI 77%–86%), and for confirmed HGD after ER were 47% (95% CI 37%–57%) and 90% (95% CI 85%–94%) respectively. Sensitivity and specificity of high risk morphology (n=124) for HGD after ER were 71% (95% CI 60%–79%) and 69% (95% CI 62%­75%) respectively. The sensitivity of high risk morphology was significantly higher than HGD on biopsy sampling (p=0.002). Detailed histopathological analysis of high risk lesions revealed invasive adenocarcinoma in 40% but a further 18% had non-invasive areas with cytological and architectural features indistinguishable from invasive adenocarcinoma. HGD was multifocal in 56%. The mean size of the focus of HGD was only 5.6 mm, and of adenocarcinoma was 11.0 mm. Mean lesion size was 53.6 mm. <h3>Conclusion</h3> Biopsy sampling of large CSNL has no value in excluding high risk lesions and morphology alone has higher sensitivity for high risk lesions. Histopathological analysis of high risk lesions reveals that areas of HGD or adenocarcinoma are very small relative to the lesion size and many contain non-invasive areas which would be cytologically indistinguishable from invasive adenocarcinoma on a biopsy. Despite this, biopsy sampling remains extremely common. Understanding of these findings and improved education regarding accurate lesion assessment may help reduce rates of inappropriate sampling.
Survivorship care planning in gynecologic oncology: Perspectives from patients, caregivers, and health care providers.
Authors: Belle Hadewijch de Rooij, Teresa Hagan, Kathryn E. Post, Jane M. Flanagan, Jeffrey M. Peppercorn, Don S. Dizon
Journal: Journal of Clinical Oncology (2018)

63 Background: More than a decade after the widespread recommendation of survivorship care plans (SCPs), evidence-based content and processes for providing survivorship care planning in gynecologic oncology remain undefined. This qualitative study sought to characterize the challenges experienced in care after treatment of gynecological cancer and preferences for survivorship care planning among patients, their caregivers and health care providers. Methods: Between July and August 2017, in-depth semi-structured interviews were conducted at a large academic hospital in the United States among patients that recently ended treatment ( &lt; 12 months) of a gynecological cancer (ovarian, endometrial, cervical and vulvar), their caregivers, and health care providers (oncologists, nurses and fellows). Main themes were identified using descriptive content analysis. Results: A total of 30 individuals participated in this study (13 patients, 9 caregivers, 8 health care providers). The vast majority of patients and caregivers (91%) expressed satisfaction for survivorship care, although all reported that remaining needs and ongoing issues remained unaddressed (i.e. distressing symptoms and mood). Almost all (95%) reported a desire for more information on how to address these needs, including issues related to side effects (59%), follow-up planning (32%), and psychological assistance (23%). Preferences for survivorship care planning differed across individuals, with respect to content, timing, and mode of delivery. Some patients did not want a SCP at all (14%). Health care providers expressed that they 1) experience challenges in communicating with patients about survivorship, 2) want to shift the focus to improving quality of life as opposed to focusing on likely disease recurrence, 3) do not currently provide formal SCPs, 4) want disease specific and tailored SCPs to support their survivorship care. Conclusions: Patients, caregivers and health care providers express a need for resources to support survivorship care in gynecologic oncology. The variation of disease types and patient and caregiver needs in this field requires multi-faceted, tailored survivorship care planning.
Integrative cluster classification to predict pathological complete response to neoadjuvant chemotherapy in early breast cancer.
Authors: Emilio Alba, Oscar M Rueda, Ana Lluch, Joan Albanell, Suet-Feung Chin, Jose Ignacio Chacon, Lourdes Calvo, Juan De La Haba, Begona Bermejo, Nuria Ribelles, Beatriz Cirauqui, Manuel Ramos Vazquez, Maria Angeles Arcusa Lanza, Eva Maria Carrasco, Jesus Herranz, Massimo Chiesa, Rosalia Caballero, Angela Santonja Climent, Federico Rojo, Carlos Caldas
Journal: Journal of Clinical Oncology (2018)

579 Background: Integrative Clustering (IntClust) is a breast cancer (BC) classification of 10 different subgroups with distinctive molecular profiles and clinical outcomes (Curtis et al., Nature 2012). We implemented an IntClust classifier based on Copy Number Alterations (CNAs) and explored its prognostic role in a cohort of pre- and post-treatment (ttm) tumors from the neoadjuvant trials GEICAM/2006-03 (NCT00432172) and GEICAM/2006-14 (NCT00841828). Methods: GEICAM/2006-03 HER2-negative pts were selectively treated according to clinical subtypes: triple negative (TN) pts with standard taxane/anthracycline-based chemotherapy (TA-CT) +/- carboplatin, and luminal A patients were randomised to TA-CT vs. hormonotherapy; GEICAM/2006-14 HER2+ pts received TA-CT + anti-HER2 therapy. Shallow-whole genome Illumina sequencing DNA data from 204 paraffin-BC (100 pre- and 104 post-ttm tumors) were used to identify CNAs and grouped samples in the 10–IntClust classification. A functional clustering by grouping IntClust 1-2-6-9 as Luminal poor prognosis (LPP), IntClust 3-4-7-8 as Luminal good prognosis (LGP), IntClust 10 (Basal-like) and IntClust 5 (HER2+) were defined. Fisher test was used to analyze IntClust distribution. Logistic regression analyses were performed to explore the association of IntClust groups with outcome (pCR in breast and axila). Results: The comparative analysis for IntClust groups in pre- vs post-ttm samples showed significantly different distribution (p = 0.01), with an enrichment of the LGP group (32% vs 55%) in the residual samples after neoadjuvant ttm, due to an increase in IntClusters 3 and 4 (both of them characterized by a low-genomic instability), and a decrease in the rest of the groups. Logistic regression analysis showed that IntClust classification in pre-ttm tumors were significant associated with pCR independently to histological grade, Ki67 and clinical subtype (p = 0.0015) Conclusions: Our data suggest an association between IntClust classification and clinical outcome in terms of pCR after neoadjuvant therapy in early BC. In our study, residual tumors after ttm were predominantly Luminal-like phenotypes with low genomic instability Clinical trial information: GEICAM/2006-03 NCT00432172. GEICAM/2006-14 NCT00841828.
Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer
Authors: Yonathan Lissanu Deribe, Yuting Sun, Christopher Terranova, Fatima Khan, Juan Martinez-Ledesma, Jason Gay, Guang Gao, Robert A. Mullinax, Tin Khor, Ningping Feng, Yu-Hsi Lin, Chia-Chin Wu, Claudia Reyes, Qian Peng, Frederick Robinson, Akira Inoue, Veena Kochat, Chang-Gong Liu, John M. Asara, Cesar Moran, Florian Muller, Jing Wang, Bingliang Fang, Vali Papadimitrakopoulou, Ignacio I. Wistuba, Kunal Rai, Joseph Marszalek, P. Andrew Futreal
Journal: Nature Medicine (2018)
Response to Single Low-dose <sup>177</sup>Lu-DOTA-EB-TATE Treatment in Patients with Advanced Neuroendocrine Neoplasm: A Prospective Pilot Study
Authors: Hao Wang, Yuejuan Cheng, Jingjing Zhang, Jie Zang, Hui Li, Qingxing Liu, Jingnan Wang, Orit Jacobson, Fang Li, Zhaohui Zhu, Xiaoyuan Chen
Journal: Theranostics (2018)

Objective:177Lu-DOTA-EB-TATE is a theranostic agent based on octreotate that uses an Evans blue structure to bind albumin to improve the pharmacokinetics and pharmacodynamics. This pilot study aims to evaluate the efficacy of a single low-dose treatment using 177Lu-DOTA-EB-TATE in patients with advanced neuroendocrine neoplasm (NEN). Methods: With IRB approval and informed consent, 4 NEN patients were enrolled to undergo 177Lu-DOTA-EB-TATE treatment with a single low dose of 0.66 ± 0.06 GBq (17.8 ± 1.7 mCi); 3 other NEN patients were enrolled as controls to undergo 177Lu-DOTA-TATE treatment with administered activity of 3.98 ± 0.17 GBq (107.6 ± 4.6 mCi). One primary tumor and 62 metastatic lesions in the 7 patients were evaluated by 68Ga-DOTA-TATE PET/CT immediately before and one or three months after the treatment. Maximum SUV (SUVmax) of the tumors ≥2.0 cm in diameter were measured and percentage of change (ΔSUV) after treatment were calculated. Results: All 4 patients subjected to 177Lu-DOTA-EB-TATE treatment tolerated the administered activity without significant adverse effects and showed symptomatic remission. Among the patients, 40 tumors were found with diameter ≥2.0 cm, with the baseline SUVmax varied from 1.5-82.9 (35.9 ± 21.0) and the ΔSUVs before and three months after the treatment from -75.1-26.3% (-38.9 ± 25.5%). Twenty-nine (72.5%) of the tumors showed >15% decrease of SUVmax (ΔSUV = -75.1%--17.1%). There was a significant negative correlation between the baseline SUVmax and the ΔSUV after treatment (r = -0.852, P < 0.001). Compared with the control 177Lu-DOTA-TATE therapy, the 177Lu-DOTA-EB-TATE treatment using approximately 1/6 the dose showed no significant difference in ΔSUV (-7.9 ± 5.4% vs. -5.8 ± 3.9%, P = 0.189) as demonstrated by the tumors with comparable baseline SUVmax from 10.0-35.0. Conclusion: A single low-dose 177Lu-DOTA-EB-TATE treatment appears to be safe and effective in the treatment of NENs with high 68Ga-DOTA-TATE uptake. This pilot study merits further investigation with increased dose and frequency of 177Lu-DOTA-EB-TATE administration with potential advantages over 177Lu-DOTA-TATE.
Reptin drives tumour progression and resistance to chemotherapy in nonsmall cell lung cancer
Authors: Jan-Henrik Mikesch, Daniela Schwammbach, Wolfgang Hartmann, Lars H. Schmidt, Christoph Schliemann, Linus Angenendt, Rainer Wiewrodt, Alessandro Marra, Nils H. Thoennissen, Eva Wardelmann, Gabriele Köhler, Georg Lenz, Carsten Müller-Tidow, Wolfgang E. Berdel, Maria-Francisca Arteaga
Journal: European Respiratory Journal (2018)

While targeted nonsmall cell lung cancer (NSCLC) therapies have improved the outcome of defined disease subtypes, prognosis for most patients remains poor. We found the AAA+ ATPase Reptin to be highly expressed in the vast majority of 278 NSCLC tumour samples. Thus, the objective of the study was to assess the role of Reptin in NSCLC. Survival analyses of 1145 NSCLC patients revealed that high RNA expression levels of Reptin are associated with adverse outcome. Knockdown of Reptin in human NSCLC cells impaired growth ex vivo and eliminated engraftment in a xenograft model. Reptin directly interacted with histone deacetylase 1 (HDAC1) as the critical mechanism driving NSCLC tumour progression. Pharmacological disruption of the Reptin/HDAC1 complex resulted in a substantial decrease in NSCLC cell proliferation and induced significant sensitisation to cisplatin. Our results identify Reptin as a novel independent prognostic factor and as a key regulator mediating proliferation and clonal growth of human NSCLC cells ex vivo and in vivo . We unveil a Reptin/HDAC1 protein complex whose pharmacological disruption sensitises NSCLC cells to cisplatin, suggesting this approach for application in clinical trials.