tbuckley/cabot-search huggingface dataset:
Zero Cases of Guinea Worm Disease in Mali
Authors: M.J. Friedrich
Journal: JAMA (2017)

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Defining response criteria in CLL patients treated in clinical research trials
Authors: Michael Hallek, Bruce D. Cheson, Daniel Catovsky, Federico Caligaris-Cappio, Guillaume Dighiero, Hartmut Döhner, Peter Hillmen, Michael J. Keating, Emili Montserrat, Kanti R. Rai, Thomas J. Kipps
Journal: Blood (2010)
A phase I study of pazopanib (P) combined with bevacizumab (B) in patients with metastatic renal cell carcinoma (mRCC) or other advanced refractory tumors.
Authors: Sylvie Negrier, David Pérol, Rastilav Bahleda, Antoine Hollebecque, Etienne Chatelut, Helen Jane Boyle, Philippe A Cassier, Celine Ferlay, Severine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard J. Escudier
Journal: Journal of Clinical Oncology (2012)

4614 Background: Since previous experiments of B with VEGFR tyrosine kinase inhibitors showed overlapping and limiting toxicities, a dose-finding study was designed to explore the safety and feasibility of the combination of a new VEGFR inhibitor P with B, in mRCC treatment-naive patients (pts) or in pts with other advanced refractory solid tumors. Methods: This bicentric trial is conducted with 3+3+3 escalation doses of P + B. The MTD is the highest dosage not expected to cause a dose limiting toxicity (DLT) in more than 2/3, 3/6 or finally 3/9 pts, during the first 8 weeks of treatment. The effect of B on steady-state pharmacokinetic (PK) of P is also investigated. Major inclusion criteria are: ECOG PS ≤1, ALT and AST &lt;=2.5 x ULN, serum creatinine &lt;=1.5 mg/dL or creatinine clearance &lt;=50 mL/mn and absence of uncontrolled hypertension. Results: 15 pts were enrolled with mRCC (n=7), melanoma (n=2), adrenocortical carcinoma (n=1), mesothelioma (n=1), pancreatic cancer (n=1), oesophageal cancer (n=1), bladder cancer (n=1) and seminoma (n=1). Median age is 61 (43-78), 12 pts are male. No DLT were reported at DL1 (P 400 mg/d + B 7.5 mg/kg q2w) (n = 9), or at the first step of DL2 (P 600 mg/d + B 7.5 mg/kg q2) (n=3), but the 3 following nephrectomized pts experienced DLT: a grade 3 transaminitis, a grade 3 pulmonary embolism and a reversible microangiopathic hemolytic anemia. Inclusion of nephrectomized pts was completed, but enrolment of 3 additional non-nephrectomized pts at DL2 was approved by IDSMB in November 2011 and these treatments are ongoing. Preliminary results of PK analysis showed a significantly higher P AUC at steady-state in pts with DLT. Moreover, lower P apparent clearance was observed in nephrectomized pts. Conclusions: The MTD of the combination of P and B is 400 mg/d and 7.5mg/kg respectively, in nephrectomized patients, but is not yet reached in other patients. Unexpected effect of nephrectomy status was observed on P pharmacokinetics.
The impact of Gleason pattern 4 ratio on recurrence following radical prostatectomy in Japanese patients with prostate cancer.
Authors: Masashi Kato
Journal: Journal of Clinical Oncology (2017)

114 Background: The 2014 International Society of Urological Pathology (ISUP) classified the Gleason grade into five groups and the Gleason score (GS) 7 was divided into groups 2 (GS3+4) and 3 (GS4+3). The ISUP recommended recording the Gleason pattern (GP) 4 ratio. However, no data are available on Japanese patients, and no studies have reported any difference between GS3+3 and a part of GS3+4. In this study, we evaluated the effect of the GP 4 ratio on recurrence following radical prostatectomy in Japanese patients with prostate cancer and revealed the equivalent between GS3+3 and part of GS3+4. Methods: We retrospectively evaluated 1,000 patients with prostate cancer who underwent radical prostatectomy at the author’s affiliated hospitals between 2005 and 2013. All prostatectomy specimen slides were reviewed by a single genitourinary pathologist according to ISUP 2014. Recurrence following radical prostatectomy was defined according to American Urological Association guidelines. The endpoint was defined as an increase in prostate-specific antigen (PSA) level. Results: Median patient age was 67 years (range, 42–77 years). Median serum PSA level was 6.8 ng/mL (range, 0.4–82 ng/mL). Median follow-up period was 59 months (range, 0.2–134 months). PSA progression was observed in 13.9% of pT2, 39.5% of pT3a, and 59.5% of pT3b. There were 164 group 1 cases (GS6), 484 group 2 (GS3+4), 212 group 3 (GS4+3), 39 group 4 (GS8), and 95 group 5 (GS9–10) cases. PSA progression-free survival was significantly different among the five groups (log rank; P = 0.0001). A significant difference was observed among the four groups with regard to the proportion by which the GP4 ratio increased (P = 0.0001) when groups 2 and 3 were divided by the GP4 ratio ( &lt; 20%, 236 cases; 20–50%, 240 cases; 51–80%, 188 cases; and 81–100%, 17 cases). On the other hand, no difference was detected between GS3+3 and GS3+4 (GS4 &lt; 20%) (P = 0.481). Conclusions: An increase in the GP4 ratio was correlated with PSA progression following radical prostatectomy in Japanese patients with prostate cancer. In addition, no difference was observed between GS3+3 and GS3+4 (GP4 &lt; 20%), and GS3+4 (GP4 &lt; 20%) patients may be an indication for active surveillance.
The effect of comorbidity on stage-specific survival in resected non-small cell lung cancer patients.
Authors: MARK Krasnik, Margreet Lüchtenborg, Erik Jakobsen, Karen Linklater, Anders Mellemgaard, Henrik Møller
Journal: Journal of Clinical Oncology (2012)

7026 Background: TNM classification has been the traditional cornerstone of decision-making in treatment choices of lung cancer. In addition to TNM stage and lung function, there is no other objective information to support this decision. Severe comorbidity affects overall survival, and may be an independent prognostic factor. In this study we quantified the effect of comorbidity on stage-specific survival in resected non-small cell lung cancer (NSCLC) patients in a large population-based setting. Methods: Among 3,152 NSCLC patients from the Danish Lung Cancer Registry who underwent surgical resection between 1 January 2005 and 31 December 2010, mortality hazard ratios were calculated during three consecutive time periods following surgery (0-1 month, 1 month - 1 year and &gt;1 year) according to Charlson comorbidity score (CCS 0, 1-2, 3+), ECOG performance status, lung function, age, sex, pathological T and N stage according to the revised 7th edition TNM lung cancer staging system, using Cox proportional hazard modelling. The Kaplan-Meier method was used to describe stage-specific survival according to the Charlson comorbidity score. Results: Increasing severity of comorbidity was independently associated with significantly higher death rates throughout the three periods of follow-up [HR1.18 for CCS 1-2 and 2.06 for CCS 3+ in 0-1 month, 1.13 for CCS 1-2 and 1.57 for CCS 3+ during 1 month - 1 year and 1.14 for CCS 1-2 and 1.84 for CCS 3+ after 1 year]. Stage-specific five-year survival in patients with severe comorbidity (CCS 3+) was significantly lower than in patients without comorbid disease [e.g., 38% (95% CI 23-53%) for pT1 and CCS 3+ vs. 69% (62-75%) for pT1 and CCS 0]. Conclusions: This study shows that severe comorbidity affects survival of NSCLC patients undergoing surgical resection by as much as a single stage increment. As the survival of NSCLC patients after different treatment regiments is mainly based on the TNM classification, further research is necessary to fully identify which patients are most likely to benefit from surgery, but also to provide a basis for developing a better prediction instrument for the survival after combination treatment involving radiotherapy and chemotherapy.
Is nitrogen mustard contamination responsible for the reported MT-45 toxicity?
Authors: J.V. Wallach, H. Morris, S.D. Brandt
Journal: British Journal of Dermatology (2017)

Helander et al. are commended for disseminating their case reports in the recent publication entitled “Acute skin and hair symptoms followed by severe, delayed eye complications in subjects using the synthetic opioid MT-45″.1 We have followed reports of side effects associated with MT-45 use for several years and the above publication serves as an important reminder of the risks of harm involved in the unregulated use of new psychoactive substances.
A randomized, double-blind, placebo-controlled multicenter phase II study of the COX-2 inhibitor apricoxib (A) in combination with either docetaxel (doc) or pemetrexed (pem) in advanced non-small cell lung cancer (NSCLC) patients (pts) selected by urinary PGE-m suppression.
Authors: Martin J. Edelman, Ming Tony Tan, Mary J. Fidler, Rachel E. Sanborn, Gregory Alan Otterson, Lecia V. Sequist, Tracey L. Evans, Bryan J. Schneider, Roger Keresztes, John S. Rogers, Jorge Antunez de Mayolo, Michelle Medeiros, Sara L. Zaknoen
Journal: Journal of Clinical Oncology (2012)

7546 Background: Overexpression of COX-2 has been associated with advanced stage and worse outcomes in NSCLC, possibly due to elevated levels of the COX-2 dependent prostaglandin, PGE-2. COX-2 inhibitors in addition to standard therapy has been associated with superior outcome in pts in whom the urinary metabolite of PGE-2, PGE-M is suppressed by the inhibitor. We hypothesized that pts defined by PGE-M suppression would benefit from the addition of apr to doc or pem. Methods: Pts with NSCLC, progressive after one platinum based therapy, PS 0-1, normal organ function, alb ≥2.5, CCr ≥ 45 were eligible for screening. A 5 day run in period with apr 400mg qd was performed. Only pts with a ≥ 50% decrease in urinary PGE-M could actually enroll. Chemotherapy was doc 75 mg/m 2 or pem 500 mg/m 2 q21 d per the investigator plus apr/placebo (P) 400 mg qd. The primary endpoint was progression free survival (PFS). Results: A total of 109 pts were screened of whom 72 demonstrated ≥50% suppression and enrolled (table). Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib vs. placebo. By chemotherapy assignment: pem/apr vs. pem/P : 103 days vs. 98 (p =.49); doc/apr vs. doc/P: 75 vs. 97 (p=.18). An adverse interaction between baseline PGE-M and doc was seen in survival (p=.026); each unit increase in urinary PGE-M increased the HR by 1.014 (p &lt; 0.038 ) vs. pem (HR =.990, p=n.s.). There was no correlation between baseline PGE-M or magnitude of PGE-M suppression and benefit from apr. Conclusions: 1. Apr did not improve outcome despite patient selection. 2. There was a trend towards an adverse outcome when apr was combined with docetaxel, that was not evident with pemetrexed. 3. Baseline urinary PGE-M may be an adverse prognostic factor for treatment with doc. [Table: see text]
Omitted evidence undermines sexual motives explanation for attractiveness bias
Authors: Marianne LaFrance, Alice H Eagly
Journal: Behavioral and Brain Sciences (2017)

This commentary makes three points: (1) the existing evidence does not consistently favor the proposed sex difference in attractiveness preferences, nor the fitness-related outcomes of attractiveness; (2) the neglected association of perceived attractiveness and trustworthiness allowed the authors to incorrectly attribute many findings solely to attractiveness, and (3) the importance accorded attractiveness in mate preferences is culturally shaped and likely evolutionarily novel.
Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma: Final results.
Authors: Andrew David Norden, Jan Drappatz, Surasak Phuphanich, David A. Reardon, Eric T. Wong, Scott Randall Plotkin, Thomas Joseph Kaley, Jeffrey J. Raizer, Glenn Jay Lesser, Tracy Batchelor, Eudocia Quant Lee, Rameen Beroukhim, Alona Muzikansky, Lisa M. Doherty, Debra C. LaFrankie, Sandra Ruland, Katrina H. Smith, Mary Gerard, Christine Sceppa McCluskey, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2014)

2027 Background: No medical therapy for recurrent meningioma has proven effective, yet a subset of these tumors recur after surgery and radiation. A pilot study of sustained-release somatostatin yielded promising results. Pasireotide LAR is a long-acting somatostatin analog with higher affinity for most somatostatin receptor subtypes than octreotide. Methods: This was a phase II trial of monthly pasireotide LAR 60 mg IM in patients with recurrent or progressive meningioma. Patients were stratified by histology (cohort A: atypical [grade 2] and malignant [grade 3] meningiomas; cohort B: benign [WHO grade 1] meningiomas). Treatment cycles were 28 days. Restaging MRIs were performed every 3 cycles and response was assessed using Macdonald criteria. Octreotide scanning was performed at baseline. Tumor tissue was obtained for somatostatin receptor immunohistochemistry. Serum IGF-1 levels were checked serially. Results: 18 patients in cohort A and 16 in cohort B were accrued. Cohort A had median age 59 (range 39-74), 8 men (44%), median KPS 80 (range 60-100), 17 (94%) with previous radiation therapy. Cohort B had median age 52 (range 36-81), 9 men (56%), median KPS 90 (range 70-100), 11 (69%) with previous radiation therapy. There were no responses. Twelve patients in cohort A (67%) achieved stable disease for a median of 4 cycles, and 13 patients in Cohort B (81%) achieved stable disease for a median of 7 cycles. In Cohort A, PFS6 was 17% and median PFS 15 weeks (95% CI: 8-20). In Cohort B, PFS6 was 50% and median PFS 26 weeks (12-43). Toxicity was mild except for grade 3 hyperglycemia in 5 (15%) patients, grade 4 hyperglycemia in 1 (3%) patient, grade 4 hypoglycemia in 1 (3%) patient, grade 3 hypokalemia in 1 (3%) patient, grade 3 fatigue in 2 (6%) patients, grade 3 amylase elevation in 1 (3%) patient, and grade 3 lipase elevation in 2 (6%) patients. Neither octreotide uptake nor IGF-1 levels predicted outcome. Staining for sst3 was predictive of favorable OS (HR 0.44, p=0.02) and PFS (HR 0.64, p=0.04). Conclusions: Pasireotide LAR is inactive in most recurrent meningiomas. Tumors with increased sst3 expression may be particularly sensitive to pasireotide, for reasons that remain to be determined. Clinical trial information: NCT00813592.
Strong but flexible: How fundamental social motives support but sometimes also thwart favorable attractiveness biases
Authors: Maria Agthe, Jon K Maner
Journal: Behavioral and Brain Sciences (2017)

Abstract Research corroborates the notion that fundamental social motives play an important role in biases that favor attractive people. Although an adaptationist framework expects favorable social effects of good looks in most situations and contexts, it simultaneously allows for potential negative social reactions and outcomes that may be elicited by physical attractiveness in other contexts. These effects of attractiveness reflect the reproductive opportunities and threats posed by potential mates and rivals.
Correlation of intratumor gene expression heterogeneity with chemotherapy sensitivity in breast cancer.
Authors: Rene Natowicz, Tingting Jiang, Weiwei Shi, Yuan Qi, Yann Delpech, William Fraser Symmans, Lajos Pusztai
Journal: Journal of Clinical Oncology (2013)

1013 Background: The goal of this study was to develop a method to quantify intratumor heterogeneity of cancers using gene expression data. We compared gene expression heterogeneity between different molecular subtypes of breast cancer and between basal like cancers with or without pathologic complete response (pCR) to neoadjuvant chemotherapy. Methods: Affymetrix U133A gene expression data of 335 stage I-III breast cancers were analyzed. Molecular class was assigned using the PAM50 predictor. All patients received neoadjuvant chemotherapy. We measured tumor heterogeneity by the Gini index (GI) calculated individually for each case over the expression of all probe sets and random subsets. The GI was used as a metric of inequality of gene expression distributions between cases. The higher the GI, the greater the inequality of the expression distribution. Results: Basal like cancers (n=138) had greater heterogeneity than luminal cancers (n=197) (mean GI values 24.51 vs 23.05, p&lt;0.001) and luminal B (n=71) cancers had greater heterogeneity compared to Luminal A (n=126) cancers (24.49 vs 22.25, p&lt;0.001). Among the basal-like cancers, those with pCR (n=44) had significantly higher heterogeneity compared to cancers with residual disease (RD, n=94) (26.10 vs 23.77, p&lt;0.001). Significant differences in GI between cancer subtypes remained for as low 2500 randomly selected probe sets. Conclusions: Breast cancer subtypes differ in intratumor gene expression heterogeneity. Greater degree of heterogeneity correlate with greater chemotherapy sensitivity. Importantly, among basal-like cancers only the heterogeneity metric differed significantly between cases with pCR or RD but not individual genes expression values or gene signatures.
Inflammatory breast cancer: a proposed conceptual shift in the UICC–AJCC TNM staging system
Authors: Tamer M Fouad, Angelica M Gutierrez Barrera, James M Reuben, Anthony Lucci, Wendy A Woodward, Michael C Stauder, Bora Lim, Sarah M DeSnyder, Banu Arun, Babiera Gildy, Vicente Valero, Gabriel N Hortobagyi, Naoto T Ueno
Journal: The Lancet Oncology (2017)
Changes in shedding of soluble tumor necrosis factor receptors (sR1/R2) and in dynamic MRI as early predictors of outcome with NGR-hTNF.
Authors: Paolo A. Zucali, Matteo Simonelli, Fabio De Vincenzo, Armando Santoro, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2013)

e22145 Background: Dose-response curve of NGR-hTNF, a selective antivascular agent, is typically biphasic with activity shown either at low dose (LD) or high dose (HD). Receptor shedding may block drug activity. Vascular effects at LD are characterized by early vessel stabilization and late vessel damage, while at HD by rapid vessel disruption. Methods: 60 pts (median age: 61; M/F: 44/16; PS 0/≥1: 25/35; median prior lines: 3) received in 2 ph I trials NGR-hTNF at LD (0.2-1.6 µg/m 2 ; n=14) or HD (60-325 µg/m 2 ; n=46) every 3 weeks. We tested the impact of early changes (post 1st dose) in baseline-normalized plasma receptor levels (n=60) and in DCE-MRI-assessed K trans (n=49) on treatment effect, including disease control (DC, rate of pts progression free at 6 weeks by RECIST criteria) and progression free survival (PFS). Results: Baseline receptor levels were not related to outcome. Post-dosing levels of sR1 (median, 4.6 ng/mL; interquartile range, 2.8-5.7) and sR2 (8.6; 4.5-10.7) increased with dose (p&lt;.0001 for both), with median values of sR1 (0.3) and sR2 (0.5) at LD being significantly lower than those of sR1 (4.9) and sR2 (9.6) at HD (p&lt;.0001 for both). Using as cutoff the 1st quartile, low sR1 levels (≤2.8 ng/mL) correlated with improved DC (OR=4.9; p=0.01) and PFS (HR=0.30; p=.003). In low vs high groups, median DC duration was 7.4 vs 2.9 months and 6-month PFS was 29% vs 0%, respectively. By adjusting for baseline covariates (age, sex, PS and prior lines), low sR1 levels remained independently associated with better DC (p=.02) and PFS (p=.008). Similar effects were noted for sR2. Levels of sR1 (r=-0.35; p=.01) and sR2 (r=-0.27; p=.07) inversely correlated with early fractional decreases in K trans , which resulted in median values unchanged after LD (4%; p=.73) and reduced after HD (-32%; p=.009). However, K trans significantly declined over time after both LD (-24%; p=.04) and HD (-44%; p=.001). Early changes in K trans did not relate with DC as defined by RECIST, but smaller decreases in K trans were associated with longer PFS (HR=0.56; p=.04). Conclusions: NGR-hTNF at LD is associated with better outcome than at HD likely due to early effects that involve minimal receptor shedding and vessel stabilization. Clinical trial information: NCT00878111-NCT00914628.
Integration of melanoma genotyping in clinical care.
Authors: Ines Esteves Domingues Pires Da Silva, Amel Salhi, Kevin P. Lui, Naima Ismaili, Chaowei Wu, Eleazar Vega-Saenz de Miera, Richard L. Shapiro, Russell S. Berman, Anna C. Pavlick, Judy Zhong, Adriana Heguy, Iman Osman
Journal: Journal of Clinical Oncology (2014)

9095 Background: Molecularly targeted therapy is improving response rates and overall survival in subsets of melanoma patients. However, targeted therapy for “triple negative” patients (BRAF, NRAS and c-KIT wild type) is not yet defined. In addition, new evidence suggests that germline variants may have an impact in melanoma progression and response to therapy. In this study, we attempt to define the utility of a recently developed clinical assay that encompasses targeted sequencing of 50 genes with known impact on cancer progression. Methods: We used the AmpliSeq Cancer Panel HotSpot.V2 from Ion Torrent. The panel targets sequencing of Hotspot regions including 2,800 COSMIC mutations within 50 oncogenes and tumor suppressor genes. Tumor and blood germline DNAs were studied. All identified mutations were independently validated by Sanger sequencing. We then linked the molecular profile to extensive clinicopathological information including treatment and prospective clinical follow-up. Results: We examined 35 tumor samples from 33 melanoma patients (2 patients had 2 specimens). 14/35 (40%) had BRAF mutations, 12/35 (34%) had NRAS mutations (one patient had both BRAF and NRAS mutated) and 2 had c-KIT mutant tumor. Eight patients were triple negative and presented with mutations in KRAS (n=2), TP53 (n=5), ERBB4 (n=1), PI3K (n=3), RB1 (n=1), NOTCH (n=1), EZH2 (n=1), APC (n=5) and KDR (VEGFR2; n=2). We detected germline variants in TP53 (40%), KDR (34%), APC (29%), KIT (23%) and PIK3CA (14%) genes. Notably, KDR Q472H has been shown to affect VEGFR2 function. Patients with KDR Q742H had higher microvessel density, higher VEGF production and a shorter survival (15.1 months compared to 54.6 months). Conclusions: Sequencing using a validated clinical assay was informative of several targetable mutations in triple negative melanoma. Inhibitors targeting some of these mutations are already FDA approved for non-melanoma and others are currently tested in clinical trials. Our data also revealed a role of germline variant KDR Q472H in melanoma progression, that was not reported before, suggesting that further functional studies are warranted.