tbuckley/cabot-search huggingface dataset:
Correlation of miR200a expression with survival in patients with small, lymph node negative head and neck squamous cell carcinoma.
Authors: Maria Vasilakopoulou, Jason Hanna, Theodoros Rampias, Christos Perisanidis, David L. Rimm, Amanda Psyrri
Journal: Journal of Clinical Oncology (2015)

e17062 Background: MicroRNAs (miRs) are small noncoding RNAs that have been shown to play a role in oncogenesis by altering mRNA expression and modifying the molecular pathway of many cancers. In head and neck cancer, the transition from dysplasia to carcinoma has been shown to occur simultaneously with alterations of miR expression profiles, with some changes being specific to the underlying risk factor. Notably, miR200a is an important regulator of nasopharyngeal cell carcinogenesis and it is present in significantly lower levels in the saliva of oral squamous cell carcinoma patients than in control subjects. Our aim was to investigate the expression and prognostic significance of miR200a on an annotated HNSCC tissue microarray. Methods: A tissue array composed of 400 larynx cancers treated with surgery followed by radiotherapy was constructed. MiR200a expression levels were assessed using in situ hybridization in conjuction with automated quantitative protein analysis (AQUA). The objectives of this analysis were to determine the association of miR200a with efficacy outcomes OS and DFS. The univariate and multivariate Cox proportional hazards models were used to evaluate the relationship between miR200a and event-time distributions. Event-time distributions were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: Two-hundred twenty eight of 400 cases had sufficient tissue for AQUA analysis. Median survival time was 118.37 months for low and 94.63 months for high miR200a expressors, respectively. Low miR200a expression was related to a more favorable but not statistically significant outcome in both DFS (p = 0.08) and OS (p = 0.08). In multivariate analysis, after adjusting for T and N stage, low tumor miR200a expression was associated with favorable outcome for OS (p = 0.04). Interestingly, heavy smokers ( > 20cigarettes/day) had lower miR200a levels (p = 0.03). Conclusions: MiR200a was an important prognostic factor in our cohort of laryngeal cancer patients treated with surgery followed by radiotherapy. A paradoxical association between miR200a and tobacco use was noted. Validation of these results is necessary.
Subgroup analyses of a phase 1/2 study of lenvatinib (E7080), a multitargeted tyrosine kinase inhibitor, in patients (pts) with advanced hepatocellular carcinoma (HCC).
Authors: Masafumi Ikeda, Kenji Ikeda, Masatoshi Kudo, Yukio Osaki, Takuji Okusaka, Toshiyuki Tamai, Takuya Suzuki, Takashi Hisai, Hideaki Miyagishi, Kiwamu Okita, Hiromitsu Kumada
Journal: Journal of Clinical Oncology (2017)

309 Background: Lenvatinib is an oral tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRα, RET, and KIT. A phase 1/2 trial in pts (n = 46) with advanced HCC and Child-Pugh score A treated with lenvatinib 12 mg once daily showed a median overall survival (OS) of 18.7 months, and a median time to progression (TTP) of 12.8 months by investigator review and 7.4 months by independent radiologic review (IRR). Objective response rate was 37.0% as assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST). Based on these results, a phase 3 study comparing the efficacy and safety of lenvatinib versus sorafenib is ongoing. Here, we report subgroup analyses of the phase 2 part of this study. Methods: Subgroups were retrospectively analyzed by Barcelona clinic liver cancer (BCLC) staging, disease etiology, prior therapy for advanced HCC (including sorafenib), and baseline Alpha-fetoprotein (AFP) levels. Efficacy endpoints including OS and TTP by IRR were assessed for each subgroup. TTP based on mRECIST and OS were assessed from the date of study registration to progressive disease and to death, respectively. Results: Median TTP and OS for each of the relevant subgroups of baseline characteristics are shown in the table. Conclusions: Pts with advanced HCC treated with lenvatinib showed similar TTP regardless of subgroup. Although the number of patients was limited, lenvatinib treatment shows promising efficacy even in patients with hepatitis B virus. Clinical trial information: NCT00946153. [Table: see text]
Erratum: Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy
Authors: Valeria Tiranti, Carlo Viscomi, Tatjana Hildebrandt, Ivano Di Meo, Rossana Mineri, Cecilia Tiveron, Michael D Levitt, Alessandro Prelle, Gigliola Fagiolari, Marco Rimoldi, Massimo Zeviani
Journal: Nature Medicine (2009)
Left Ventricular Dysfunction Switches Mesenchymal Stromal Cells Toward an Inflammatory Phenotype and Impairs Their Reparative Properties Via Toll-Like Receptor-4
Authors: Nili Naftali-Shani, La-Paz Levin-Kotler, Dahlia Palevski, Uri Amit, David Kain, Natalie Landa, Edith Hochhauser, Jonathan Leor
Journal: Circulation (2017)

Little is known about the potentially unfavorable effects of mesenchymal stromal cell (MSC) activation on the heart. MSCs can respond to tissue injury by anti- or proinflammatory activation. We aimed to study the potential negative interaction between left ventricular dysfunction (LVD) and MSC activation.We isolated MSCs from cardiac and subcutaneous fat tissues of mice with LVD 28 days after myocardial infarction or sham operation. To evaluate the effect of LVD on MSCs, we characterized cardiac MSCs and subcutaneous MSCs in vitro. Subsequently, we injected MSCs or saline into the infarcted myocardium of mice and evaluated LV remodeling and function 28 days after myocardial infarction. To test the hypothesis that toll-like receptor 4 (TLR4) mediates proinflammatory polarization of MSCs, we characterized cardiac MSCs from TLR4-/- and wild-type (WT) mice after inflammatory stimulation in vitro. Next, we transplanted cardiac MSCs from TLR4-/- and WT male mice into the infarcted myocardium of female WT mice and evaluated infarct size, MSC retention, inflammation, remodeling, and function after 7 days.LVD switched cardiac MSCs toward an inflammatory phenotype, with increased secretion of inflammatory cytokines as well as chemokines. The effect of LVD on subcutaneous MSCs was less remarkable. Although transplantation of cardiac MSCs and subcutaneous MSCs from LVD and sham hearts did not improve LV remodeling and function, cardiac MSCs from LVD exacerbated anterior wall thinning 28 days after myocardial infarction. The inflammatory polarization of cardiac MSCs by LVD was mediated by TLR4, as we found less secretion of inflammatory cytokines and higher secretion of anti-inflammatory cytokines from activated cardiac MSCs of TLR4-deficient mice, compared with WT cardiac MSCs. Significantly, TLR4 deficiency preserved the expression of CD47 (don't eat me signal) on cardiac MSCs after both TLR4 stimulation in vitro and transplantation into the infarcted heart. Compared with WT cardiac MSCs and saline, TLR4-/- cardiac MSCs survived in the cardiac tissue and maintained their reparative properties, reduced infarct size, increased scar thickness, and attenuated LV dilatation 7 days after myocardial infarction.The environment of the failing and infarcted myocardium drives resident and transplanted MSCs toward a proinflammatory phenotype and restricts their survival and reparative effects in a mechanism mediated by TLR4.
A novel strategy to build research capacity in survivorship science.
Authors: Maria Alma Rodriguez, Maria E. Suarez-Almazor, Paula A. Lewis-Patterson, Guadalupe R. Palos
Journal: Journal of Clinical Oncology (2017)

13 Background: The steady increase in cancer survivors supports the need for robust clinical and translational survivorship research. Yet, supportive environments and infrastructures to accelerate progress in survivorship research remains relatively limited. This abstract describes the implementation and initial outcomes of an institution’s unique approach to enhance their research capacity in survivorship science. Methods: An executive leadership team championed the formation of a research infrastructure based on the survivorship translational science model. Initial funding from a philanthropic foundation supported a doctoral prepared researcher and staff to provide administrative support. A 30-member Faculty Advisory Workgroup comprised of experts from different disciplines developed a conceptual and sustainability plan. Key components focused on seed money awards, trainee and professional education, and faculty development. Outcomes were measured in 5 groups: 1) seed money - number of $50,000 seed money grants awarded, external funding obtained, publications in peer-reviewed journals, and poster presentations, 2) professional and trainee educational events, i.e. number of symposia, grand rounds, trainees, participants, 3) number and type of faculty development events, and 5) infrastructure sustainability. Descriptive statistics summarize data. Results: Accomplishments achieved from 2011 – 2016 included a return on investment of a 16:1 ratio, 16 awards granted to new investigators totaling $953, 000, funding for 9 external awards resulting in a total of $15, 437, 441, 31 peer-reviewed publications, and 54 podium/oral presentations. Professional events included 8 professional symposia (784 and 325 posters), 6 institutional grand rounds, and 25 undergraduate trainees completed a research internship. Funding to sustain this program was recently awarded. Conclusions: This approach designed to build research capacity appears effective in supporting researchers in generating new evidence which can improve survivors’ outcomes.
Patient-reported outcomes from adolescent/young adult (AYA) cancer survivors.
Authors: James M. Metz, Margaret K. Hampshire, Carolyn Vachani, Gloria A DiLullo, Christine E. Hill-Kayser
Journal: Journal of Clinical Oncology (2014)

9605 Background: AYA survivors may experience unique toxicites compared to older survivors, and these may be difficult to measure. This Internet based study evaluates patient-reported outcomes during cancer survivorship. Methods: Data were gathered via a convenience sample frame from cancer survivors voluntarily utilizing a publically available, free, Internet-based tool for creation of survivorship care plans. Available at www.livestrongcareplan.com and through the OncoLinkwebsite, it provides customized guidelines for survivor care. During use of the tool, survivors are queried regarding late effects for which they are at risk. All data have been maintained with IRB approval. Results: The tool has been used by over 35,000 persons, with PRO available for 11,301; 32% of these were AYA. Median age of AYA survivors was 30 (Range 18 – 35; median diagnosis age 27). Median age of older survivors was 54 (Range 36 – 93, median diagnosis age 50). AYA survivors were 70% female and older were 76% female. In the AYA cohort, most common cancer diagnoses were hematologic (30%), breast (25%), and genitourinary (GU) (18%), compared to breast (44%), gastrointestinal (11%), and GU (10%) in the older cohort. AYA survivors reported cognitive changes (54%), and sexual side effects most frequently. Among males, erectile dysfunction (ED) was reported by 7% of AYA survivors, all of whom denied ED prior to treatment; of these, 14% reported that they had not maintained an erection until completion of intercourse since cancer treatment, and 23% reported that they could do so about 50% of the time. Retrograde/dry ejaculation was reported by 53%. Among females, sexual concerns such as vaginal dryness and shrinkage were reported by 47%. Time since cancer diagnosis ranged from <1yr to 15 years for the AYA cohort (median 2.1 years). Conclusions: AYA survivors are prominent users of this tool, although their diagnosis profile differs from that of older users. They report significant late effects, including perceived cognitive changes and prominent sexual side effects, and these may warrant specific counseling and support.
Frequency of <i>MET</i> amplification determined by comprehensive next-generation sequencing (NGS) in multiple solid tumors and implications for use of <i>MET</i> inhibitors.
Authors: Norma Alonzo Palma, Gary A. Palmer, Siraj M. Ali, Philip J. Stephens, Jeffrey S. Ross, Vincent A. Miller, Doron Lipson
Journal: Journal of Clinical Oncology (2013)

11068 Background: MET expression has been shown to be prognostic and possibly predictive in several tumor types and both small molecule inhibitors of MET kinase as well as monoclonal antibodies are under study as therapies for this subset of patients. However, the methods to assess MET overexpression are not well standardized. In the clinic, NGS is an advanced diagnostic method for identifying known and unknown targeted-therapy options. We therefore sought to explore the ability of NGS to detect high level MET amplifications in a general oncology population. Methods: We review here the results from analysis of 2,221 FFPE tissue samples across a range of tumor types by an NGS assay in a CLIA-certified laboratory (Foundation Medicine). We specifically report base pair substitutions, small insertions/homozygous deletions (indels), high level (&gt; 6 copies/nucleus) amplification (amp) and select rearrangements in 189 genes, including MET. Results: MET was altered in 28/2,223 (1.2%) of patient samples. MET alterations were limited to amplifications (median 15X, range 6X-40X); no base pair substitutions, indels, or rearrangements were found. MET amp was present in 3/48 (6.2%) primary bone sarcomas, 1/20 (5.0%) myogenic sarcomas, 2/58 (3.4%) gastric, 1/38 (2.6%) kidney, 2/78 (2.5%) hepatocellular, 1/41 (2.4%) uterine, 4/188 (2.1%) unknown primary, 2/99 (2.0%) ovarian, 8/386 (2.0%) lung, 3/157 (1.9%) colorectal, and 1/109 (0.9%) pancreatic carcinomas. Conclusions: Use of NGS to characterize MET alterations in a 2,000 + patient population provides evidence for the role of NGS in identifying the future use of MET-targeted therapy in a variety of common and uncommon solid tumors. Clinical follow-up of the subset of cases treated with a MET inhibitor is ongoing.
A phase II study of gemcitabine, oxaliplatin, and erlotinib (GEMOX-T) combination chemotherapy in previously untreated patients with locally advanced unresectable or metastatic pancreatic cancer.
Authors: Jina Yun, Han Jo Kim, Kyoung Ha Kim, Se Hyung Kim, Hyun Jung Kim, Sang-Cheol Lee, Sang Byung Bae, Chan Kyu Kim, Namsu Lee, Kyu Taek Lee, Seong Kyu Park, Jong-Ho Won, Dae Sik Hong, Hee Sook Park, Hyun Jong Choi, Jong Ho Moon
Journal: Journal of Clinical Oncology (2014)

e15260 Background: In a phase III trial, the addition of erlotinib to gemcitabine improved the survival in advanced pancreatic cancer compared with gemcitabine alone. In addition, gemcitabine in combination with oxaliplatin was superior to gemcitabine alone in terms of the progression-free survival and response rate in one phase III trial. Therefore, this study evaluated the safety and activity of erlotinib with gemcitabine and oxaliplatin combination chemotherapy given as first-line therapy for locally advanced unresectable or metastatic pancreatic cancer. Methods: Patients with chemotherapy-naïve, histologically confirmed, unresectable or metastatic pancreatic cancer were given GEMOX-T (oral erlotinib 100 mg daily, gemcitabine 1000 mg/m² iv, and oxaliplatin 50 mg/m2 iv on days 1 and 8) every 3 weeks. The primary endpoint was the response rate. Results: An enrollment of 32 patients was planned, and 33 patients are registered. The patients’ median age was 58 (range 31–82) years. 29 patients were evaluable and 13 patients (45%) had partial responses. The disease control rate was 86.2%. 148 chemotherapy cycles were delivered (median, 4 ; range, 1-18). The median progression free survival was 4.8 months (95%CI: 4.1-5.5) and the median overall survival was 8.4 months (95%CI: 7.0-9.8). Generally, GEMOX-T was well tolerated. The major grade 3/4 hematological toxicities were neutropenia (20%) and anemia (17%), which were manageable. The main non-hematological toxicities were nausea (29%), anorexia (29%), rash (27%), fatigue (25%), and diarrhea (24%); these were mainly grade 1/2 (95, 86, 100, 97, and 91%, respectively). There was no treatment-related mortality. The relative dose intensities of gemcitabine, oxaliplatin, and erlotinib were 97, 97, and 100% of the planned doses, respectively. Conclusions: GEMOX-T appears to be active as first-line chemotherapy for unresectable or metastatic pancreatic cancer, and the safety profiles are acceptable. Also, the high response rates of GEMOX-T may allow initially unresectable patients to undergo resection. Clinical trial information: NCT01505413.
Interventions for Hidradenitis Suppurativa
Authors: John R. Ingram
Journal: JAMA Dermatology (2017)

<h3>Clinical Question</h3> Which treatments have been shown to be effective in randomized clinical trials (RCTs) for hidradenitis suppurativa (HS) in adults? <h3>Bottom Line</h3> There is high-quality evidence of benefit from adalimumab given weekly, while every other week dosing is ineffective, with reductions in Dermatology Life Quality Index (DLQI) scores compared with placebo of 2.8 points (95% CI, −3.7 to −2.0 points) and 1.6 points (95% CI, −3.9 to 0.6 points), respectively. Moderate-quality evidence suggests that infliximab is beneficial; RCT evidence for other interventions was lower in quality or absent, limiting further conclusions.
Survival and cause of death in patients with refractory anemias.
Authors: Yue Zhang, Bonnie Gould Rothberg, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2013)

7033 Background: Despite its common occurrence, there are few large population-based studies on low-grade myelodysplastic syndromes (MDS). We evaluated the outcomes for the two low-risk MDS subtypes. Methods: The Surveillance, Epidemiology and End Results (SEER) database was searched for patients with refractory anemia (RA) or RA with ringed sideroblasts (RARS), diagnosed between 2001 and 2009 with complete demographic information. Incidence rates were calculated from SEERStat 7.1. Overall survival (OS) and disease-specific survival (DSS) were calculated from diagnosis to death from any cause and death from MDS or acute leukemia, respectively. Univariate survival was estimated by the Kaplan-Meier method and curves compared by log rank. Univariate and multivariable Hazard ratios (HR) were calculated by Cox Proportional Hazards. Results: Among the 6,505 patients who met the inclusion criteria, there were 3,866 (59%) RA and 2,639 (41%) RARS. Age-adjusted incidence rates per 100,000 population for RA and RARS were 0.55 and 0.44 respectively. Medians OS for RA and RARS were 39 and 48 months respectively. Although RARS was associated with improved 5-year OS compared to RA (41.3% vs 37.7%; HR 0.86; 95% CI 0.81-0.92, p &lt; 0.0001), there were no differences in 5-year DSS (74.2% vs 76.3%; HR 1.01, 95% CI 0.90-1.14, p = 0.41). Altogether, 2,112 deaths were accrued among RA patients and 1,352 among the RARS subclass. The number of deaths due to MDS or acute leukemia were 610 (28.8%) in RA and 457 (33.8%) in RARS. Acute leukemia was the cause of death in 190 (9.0%) RA patients and in 143 (10.6%) of RARS patients. Cardiovascular disease accounted for 25% of total deaths in RA and RARS. After adjusted for age, gender, race and year of diagnosis, RARS was associated with increased OS (HR 0.81; 0.76-0.87; p &lt; 0.0001) but not DSS (HR 0.95; 0.84-1.07, p = 0.41). Conclusions: Both RA and RARS are indolent diseases with a high 5-year DSS and death occurring mostly from other causes, particularly cardiovascular disease. Although RARS was associated with better 5-year OS compared to RA, there were no differences in 5-year DSS.
Endoscopic ultrasound-guided hemostasis of rectal varices
Authors: Tanima Jana, Tejal Mistry, Shashideep Singhal
Journal: Endoscopy (2017)

The prevalence of rectal varices in patients with cirrhosis ranges from 38 % to 56 % [1]. While lower gastrointestinal endoscopy can help diagnose rectal varices, endoscopic ultrasound (EUS) may be more accurate in patients with smaller varices [1]. Reports are limited, but techniques for EUS-guided hemostasis of rectal varices include: injection sclerotherapy [2], band ligation [3], embolization with coils [4], and glue injection [4] [5]. Interventional radiology procedures, such as transjugular intrahepatic portosystemic shunting and balloon-occluded retrograde transvenous obliteration, are helpful only in selected patients. Here we describe a unique case of EUS-guided hemostasis of rectal varices using coils and glue.
Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial
Authors: James L Gulley, Arun Rajan, David R Spigel, Nicholas Iannotti, Jason Chandler, Deborah J L Wong, Joseph Leach, W Jeff Edenfield, Ding Wang, Hans Juergen Grote, Anja von Heydebreck, Kevin Chin, Jean-Marie Cuillerot, Karen Kelly
Journal: The Lancet Oncology (2017)
A phase (Ph) I/II study of belinostat (Bel) in combination with cisplatin, doxorubicin, and cyclophosphamide (PAC) in the first-line treatment of advanced or recurrent thymic malignancies.
Authors: Anish Thomas, Arun Rajan, Sean Khozin, Eva Szabo, Corey Allan Carter, Udayan Guha, Michell Manu, Arlene W Berman, Tricia Kunst, Richard Piekarz, David S. Schrump, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2012)

7103 Background: Belinostat is a hydroxamic acid histone deacetylase (HDAC) pan-inhibitor with single agent activity in thymic malignancies. PAC has activity against thymic cancers. Synergy between Bel and several chemotherapeutic agents, including P, A, and C, has been demonstrated in preclinical models. Methods: Patients with histologically confirmed, treatment naive advanced thymic malignancies, PS&lt;2, measurable disease, and adequate renal, hepatic and hematopoietic functions were eligible. Ph1 evaluated safety and tolerability of the combination using increasing dose levels (DL) of Bel (1000-2000 mg/m² over 48 h CIVI) and PAC (50/50/500 mg/m² IV/cycle) (3+3 dose escalation schema), administered every 21 days for no more than 6 cycles followed by optional maintenance Bel every 4 weeks. Primary end point of Ph2 is overall response rate (ORR). Results: From March 2010 to January 2012, 13 patients were enrolled [7 thymoma (T), 6 thymic carcinoma (TC); 8 in Ph1 and 5 in Ph2; median age: 49 years (range, 23-76)]. In Ph1, 6 patients were treated at DL1 (Bel 1000 mg/m 2 + PAC) and 2 patients at DL2 (Bel 2000 mg/m 2 + PAC). Dose Limiting Toxicities were Grade 3 nausea and diarrhea, and Grade 4 neutropenia and thrombocytopenia. Recommended phase II dose (RP2D) was set at DL1. Most common grade 3/4 treatment-related adverse events (AE) were lymphocytopenia (100%), leucopenia (85%), neutropenia (77%) thrombocytopenia (54%), anemia (38%), hypophosphatemia (38%), hypomagnesemia, hypokalemia, elevated AST, prolonged QTc and infusion-catheter related thromboembolic complications (23% each). Outcomes included one complete response (CR; T at DL1), 6 partial responses (PR; 4 T, 2 TC; 4 in Ph1, 2 in Ph2) and 6 stable disease (SD; 2 T, 4 TC; 3 each in Ph1 and Ph2). Four patients previously deemed unresectable underwent surgical resection. Conclusions: Belinostat in combination with PAC has activity in thymic malignancies with a predicable AE profile. ORR was 54% including 33% PR in the TC subgroup. RP2D of the combination has been defined. Accrual to Ph2 part and molecular profiling of patient tumors is ongoing.