tbuckley/cabot-search huggingface dataset:
Evaluating oncogenic pathway dysregulation in adolescents and young adults with acute myeloid leukemia.
Authors: Arati Rao, John Andy Livingston, Sandeep S. Dave
Journal: Journal of Clinical Oncology (2013)

7107 Background: Adolescent and young adults (AYAs) with Acute Myeloid Leukemia (AML) have been shown to have better outcomes with induction chemotherapy when compared to older young adults (OYAs). Multiple psychosocial, treatment, and host-related factors unique to AYAs have been identified but the contribution of disease biology to these outcomes has not yet been fully characterized. The purpose of this study was to evaluate disease biology as it relates to age-specific differences in outcomes for AYAs with AML. Methods: Clinically annotated, microarray data from 425 patients with newly diagnosed AML from two publicly available datasets: GSE1159; and GSE12417 were analyzed. Age-specific cohorts (AYAs ≤ 30 years; n = 58 and OYAs &gt;30 but ≤ 60 years; n=276) were prospectively identified. Patients in GSE1159 were treated according to protocols of the Dutch–Belgian Hematology–Oncology Cooperative group and included 111 patients who ultimately underwent stem-cell transplantation. Patients in GSE12417 were treated per the AMLCG-1999 protocol. Gene expression analysis was conducted by applying previously defined and tested signature profiles reflecting deregulation of oncogenic signaling pathways and altered tumor environment. All statistical analysis was performed using S-plus and survival analysis by Cox proportional-hazards regression was used to assess differences in overall survival (OS) between age-specified study cohorts and a one-sided p-value ≤ 0.05 was considered statistically significant. Results: AYA patients had a significantly better OS (median survival 24.1 months vs. 13.0 months in OYAs; p=0.0285), but there was no difference in Event Free Survival (p=0.23). Analysis of oncogenic pathways revealed that AYA patients likely had better OS because of lower TNF (p=0.03) and higher myc (p=0.02) pathway activation. Conclusions: AML arising in AYAs may represent a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that contributes to OS. We hope these findings will enable clinically meaningful adjustments of treatment strategies in the AYA AML patient population.
Comparison of Demographic and Photobiological Features of Chronic Actinic Dermatitis in Patients With Lighter vs Darker Skin Types
Authors: Ki-Wei Tan, Ann K. Haylett, Tsui C. Ling, Lesley E. Rhodes
Journal: JAMA Dermatology (2017)

Chronic actinic dermatitis (CAD) is classically described in older, white men, although increasing reports describe younger patients with darker skin types, particularly South Asians. Photocontact allergy occurs in CAD but is less studied than contact allergy in this exquisitely photosensitive condition.To evaluate for differences in demographic and photobiological features between persons with darker and lighter skin types who have CAD.This retrospective review included 70 consecutive adult patients (≥18 years) undergoing investigation for photosensitivity who were diagnosed with CAD from November 1, 2000, through August 31, 2015, at the specialist Photobiology Unit of a tertiary academic referral center.Patient age, sex, ethnicity, clinical features, and phototesting outcomes.A total of 70 patients (37 men [53%] and 33 women [47%]; mean [SD] age, 50.9 [2.3] years) were diagnosed with CAD. Of these, 36 were non-Hispanic and non-Latino white, 31 were Asian (including 24 South Asian, 4 East Asian, and 3 Middle Eastern), and 3 were black. Patients were aged 9 to 83 years at diagnosis, with a mean (SD) age at onset of 42.6 (2.4) years and duration of disease of 8.8 (1.3) years. Forty-one had lighter skin types (Fitzpatrick skin types I-IV), and 29 had darker skin types (Fitzpatrick skin types V and VI). Patients with darker skin types and CAD were younger at diagnosis (mean [SD] age, 40.7 [3.5] vs 58.1 [2.5] years; P < . 001) and had earlier onset of photosensitivity (mean [SD] age, 35.5 [3.9] vs 47.5 [2.9] years; P = .01) compared with patients with lighter skin types. Of note, the male to female ratio in the lighter skin group was 2:1 compared with 1:2 in the darker skin group. Phototest reactions were equally severe in Fitzpatrick skin types V to VI and I to IV, with minimal erythemal doses to monochromatic UV-B, UV-A, and visible radiation and broadband provocation testing showing similar results. Photoallergic contact reactions to UV filters, personal sunscreen products, and nonsteroidal anti-inflammatory drugs were seen in both groups; 14 of 61 patients (23%) undergoing photopatch testing showed positive photopatch reactions.Chronic actinic dermatitis presents with an earlier age at onset and an inverted male to female ratio in patients with darker compared with lighter skin types. Clinicians should thus be cognizant of CAD in younger women with darker skin types. Photopatch testing should be considered in patients with CAD, with coexistent photocontact allergy occurring in a substantial proportion.
Comanagement and emergency room admissions in oncology practice.
Authors: Jennifer Nadine Slim, Michelle Marie Loch
Journal: Journal of Clinical Oncology (2017)

21 Background: Cancer survivors face many challenges and encompass a multitude of specialties. These patients frequently utilize emergency room services with increased admission rates and, often, significant consequences on health care costs. National Hospital Ambulatory Medical Care Survey data from 2011 reports non-ischemic heart disease, chest pain and pneumonia as the most common emergency room discharge diagnoses for adults. We hypothesized that cancer survivors who continue care with primary providers require fewer emergency room based admissions. Our purpose in identifying these demographics was to allow for further consideration of specific interventions that might improve out patient based management. Methods: We considered ongoing primary care as those assigned to a primary care provider. We developed a memorandum of intention to identify patients at risk for over utilization of emergency room services. We gathered anonymous data about oncology patients seen in clinic from July 2014 to August 2015. We were able to determine how many emergency room based admissions were attributed to these patients as well as patients with and without primary care providers assigned in the EMR. We further attempted to identify those at higher risk taking into account co-morbid diagnoses. Results: 2,627 survivors were seen in clinic with 163 emergency room based admissions. 75% of these patients did not have a primary care provider identified in EPIC and account for 51% of the admissions. Only two patients had 3 or fewer co-morbid diagnoses. The most common co-morbid diagnoses among patients with emergency room based admission were abdominal pain, anemia, and chest pain. Conclusions: This data would suggest that co-management with primary care providers alone is not adequate for cancer survivors. While about half of the admissions were those without assigned primary care; the overall percentage of admission was higher from those assigned primary care providers. We suggest risk factors and management strategies are unique to survivors and require a focused multidisciplinary approach. Further study focused on interventions unique to cancer survivors are warranted.
Reducing the burden of patient reporting of physical function in the chronic care of cancer survivors through a branching logic electronic symptom survey (BLESS).
Authors: Elizabeth Hall, Mindy Liang, Emily Tam, Judy Chen, Chenchen Tian, Matthew A Campbell, Kathryn Bucci, Lin Lu, Brandon C Tse, Dennis Zheng, Lauren Wong, Samantha Sarabia, Sabrina Yeung, Gursharan Gill, Andrea Perez-Cosio, M. Catherine Brown, Wei Xu, Geoffrey Liu, Doris Howell
Journal: Journal of Clinical Oncology (2017)

5 Background: A patient’s functional status is a key outcome variable used to both measure and improve quality of care in cancer survivors. However, comprehensive research tools such as the HAQ-DI and WHODAS instruments pose 35 questions altogether, increasing patient reporting burden. We evaluated whether a BLESS could be developed with high sensitivity of screening questions followed by questions relevant to specific physical function domain, through a branching logic algorithm. Methods: Adult cancer clinic outpatients at Princess Margaret Cancer Centre used tablet technology to complete the HAQ-DI, WHODAS, EQ-5D-3L and PRO-ECOG. BLESS was developed as an algorithm that used PRO-ECOG/EQ-5D-3L to screen for appropriate domains of HAQ-DI/WHODAS to query. Sensitivity/specificity of BLESS screeners to HAQ-DI/WHODAS items were reported. BLESS derived physical function scores were also compared to scores generated by the full version of WHODAS/HAQ-DI. Results: Of 407 patients,median age was 62 (range 20-93) years, 51% female, 75% Caucasian, with a median EQ-5D-3L index score of 0.83 (0.31-1.00), and WHODAS of 6.0 (0-37). Of cancer sites, 14% had breast, 11% GI, 11% GU, 18% head/neck, 10% thoracic, 18% hematologic, and 15% gynecologic cancers. 34% were stage III-IV; 72% were treated for curative intent. Using the sum of mobility, self-care, and usual activities dimensions of the EQ-5D-3L to dichotomize patients as with or without difficulty, we found an area under the receiver operating curves that was &gt; 90% when comparing to recommended WHODAS and HAQ cut-offs for significant physical dysfunction. Using BLESS, 38% of our clinic outpatients need answer only 5 questions, generating derived-WHODAS scores with no median difference when compared to reported scores; sensitivity of screeners for each WHODAS/HAQ-DI item ranged from 92-100%. Overall, median number of questions asked was 9. Conclusions: By focusing on relevance, BLESS maintained high sensitivity with a dramatic decrease in question burden compared to traditional research surveys for physical function. BLESS is suitable for use in immediate, routine screening of chronic care outcomes.
The prognostic importance of miRNA-21 in stage II colon cancer: A population-based study.
Authors: Sanne Kjaer-Frifeldt, Torben Hansen, Boye Schnack Nielsen, Stine Joergensen, Jan Lindebjerg, Flemming Brandt Sorensen, Rene dePont Christensen, Anders Kristian Moeller Jakobsen
Journal: Journal of Clinical Oncology (2012)

3513 Background: Adjuvant chemotherapy for stage II colon cancer patients is still controversial and the debate on which patients should be considered as high risk patients is still ongoing. The decision is based on clinical and pathological markers of risk, which are inadequately informative in most of the patients, and better methods are highly needed. The aim of the present study was to investigate the possible prognostic importance of miRNA-21, quantified by in situ hybridization (ISH), in a unique, large population-based cohort of patients treated for stage II colon cancer patients. Methods: The study included all patients diagnosed with stage II colon cancer in Denmark in the year 2003 (711 patients), representing a full population of five million people. Patients receiving adjuvant chemotherapy were excluded (N=15). One paraffin-embedded tissue block was obtained from each patient. A 6μm-thick section was processed for formazan-based chromogenic miR-21 ISH analysis and counter stained with nuclear red. The blue miR-21 ISH signal was assessed by image analysis to obtain two quantitative expression estimates: the total blue area (TB) and the ratio of TB with the nuclear density (TBR). Results: The miRNA-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. Patients expressing high levels of miRNA-21 (high mean TBR) had significantly inferior cancer specific survival (CSS): HR = 1.26 (95% CI; 1.15-1.60), p &lt;0.001. In the COX regression analysis (including; gender, T-category, malignancy grade, localization, tumor perforation, tumor fixation, number of lymph nodes and MSI status), mean TBR was found to be an independent predictive marker of poor CSS, HR = 1.41 (95%CI; 1.19-1.67, p&lt; 0.001). The same applied to TB. Conclusions: The present study shows that increasing miRNA-21 expression level is significantly correlated to decreasing CSS. Analyses of miRNA-21 should be considered as a potential adjunct in the selection of high risk stage II patients.
Comparing elderly and non-elderly adult cancer survivors: Differences in modifiable behaviours of smoking and alcohol cessation and physical activity.
Authors: Chongya Niu, Lawson Eng, Xin Qiu, Xiaowei Shen, Osvaldo Espin-Garcia, Dan Pringle, Mary Mahler, Oleksandr Halytskyy, Rebecca Charow, Christine Lam, Ravi M. Shani, Jodie Villeneuve, Kyoko Tiessen, M Catherine Brown, Peter Selby, Doris Howell, Jennifer M. Jones, Wei Xu, Shabbir M.H. Alibhai, Geoffrey Liu
Journal: Journal of Clinical Oncology (2013)

9551 Background: In developing a cancer survivorship program at Princess Margaret Cancer Centre (Canada), cancer survivors were surveyed on modifiable behaviours: smoking/alcohol intake and physical activity. We evaluated whether special considerations should be given to elderly cancer survivors (age 65 years or higher), where few data currently exists. Methods: 616 adult cancer survivors of all disease sites were asked about their smoking, alcohol, and physical activity habits, and their attitudes and knowledge about effects of these habits on cancer outcomes. Univariate and multivariate logistic regression models evaluated the effect of age on these factors. Results: 23% were elderly; 53% female; 15% breast, 20% gastrointestinal/gynecologic, 24% hematologic, 19% thoracic/head and neck, and 13% genitourinary cancers. Median follow up was 24 months. Elderly survivors were more likely to be ever smokers (OR=1.69, 95% CI [1.12-2.53]) and ex-smokers than current (OR=4.11 [2.02-8.33]), but less likely to know how smoking could affect cancer treatment (OR=1.72 [1.09-2.69]) or outcome (OR=1.66 [1.07-2.60]). Elderly patients were less likely to binge drink (OR=2.07 [1.34-3.19]), but more likely to perceive alcohol as improving quality of life (OR=1.98 [1.11-3.56]) and overall survival (OR=2.32 [1.22-4.41]) in their own situation. Elderly survivors were less likely to receive information about alcohol use (OR=2.89 [1.29-6.49]). Meeting exercise guidelines at diagnosis (OR=1.76 [1.16-2.67]) and improving/maintaining them after treatment (OR=2.02 [1.12-2.93]) was substantially lower in elderly survivors, but perceived benefits/harms of exercise did not differ with age. Conclusions: Elderly patients know less about the impact of smoking on their overall health, despite having higher rates of cumulative exposure. A lower proportion received information on alcohol use. Elderly patients are less able to achieve the same exercise goals as younger patients. Survivorship programs may need to tailor counselling on modifiable behaviours by age group. CN, LE, SMHA, and GL contributed equally.
A phase I study of convection-enhanced delivery of nanoliposomal irinotecan using real-time imaging in patients with recurrent high grade glioma.
Authors: Nicholas A. Butowski, Seunggu Han, Jennie Webster Taylor, Manish K. Aghi, Michael Prados, Susan Marina Chang, Jennifer Leigh Clarke, Krys Bankiewicz, Daryl C. Drummond, Jonathan Fitzgerald
Journal: Journal of Clinical Oncology (2015)

TPS2081 Background: Cytotoxic drug delivery to high grade glioma (HGG) is limited by the blood brain barrier (BBB). Convection-enhanced delivery (CED) improves chemotherapy delivery by utilizing fluid convection, obviating the challenges of crossing the BBB while minimizing systemic toxicity. CED of a highly concentrated formulation of nanoliposomal irinotecan (MM-398, nal-IRI) has been optimized in animal models of brain tumors and shows superior anti-tumor activity compared to systemic delivery. A major advance in the application of CED is the development of real time CED, which utilizes an interventional MRI suite to visualize the CED process with the aid of a co-convected contrast agent, and thus allows for real time monitoring of drug delivery to the target. Methods: With support from a R21 grant, a Phase I study of CED of concentrated nal-IRI using real-time imaging in patients with recurrent HGG is currently open for enrollment. This is a 3+3 dose escalation trial, with dose levels of 20 mg, 40 mg, 60 mg, and 80 mg of nal-IRI, given via up to 3 catheters surgically placed in an intra-tumoral location. The MRI contrast agent gadoteridol (2 mM) will be co-infused via the same catheters. Interim safety, efficacy, and imaging response results will be presented. From the imaging data, the correlation of pre-infusion modeling of drug distribution with post-infusion imaging will be analyzed. This will also allow for determination of the total volume of distribution to volume of infusion (Vd:Vi) ratio for each infusion. Clinical trial information: NCT02022644.
Proliferation and apoptosis before and after primary systemic therapy for operable breast cancer
Authors: V. Guarneri, F. Piacentini, A. Frassoldati, G. Ficarra, G. Jovic, F. Puglisi, A. Michelotti, G. Bisagni, R. Berardi, P. Conte
Journal: Journal of Clinical Oncology (2007)

21045 Background: The identification of biological markers able to predict tumor sensitivity to primary systemic therapy (PST) may have an important clinical output. Moreover, the effect of treatment on these biomarkers might have prognostic relevance. Aims of this analysis: to evaluate the predictive role of proliferation (Ki-67), apoptotic index (AI) and growth index (GI) before PST, the effect of PST on these parameters and their relation with tumor response and patients outcome. Methods: Ki-67, AI (Tunel Test), and GI were assessed at baseline and at surgery in 90 stage II-IIIB breast cancer patients enrolled in a phase II randomized trial of PST with 4 cycles of epirubicin-paclitaxel ± gefitinib. Pathologic response was defined as tumor regression grade (TRG) (criteria of Miller and Payne). Results: patients characteristics were as follows: median age, 51 yrs (range 29–69); stage IIA 41%, IIB-IIIA 59%. A significant correlation between Ki-67 and AI was found at baseline (p=0.001). A significantly higher Ki-67 and AI were observed in ER- vs ER+ tumors (median Ki-67: 62% vs 25%, p&lt;0.0001; median AI: 1.33 vs 0.85, p=0.009). A significantly higher Ki-67 and GI were observed in EGFR+ vs EGFR- tumors (median Ki-67: 60% vs 25%, p=0.0006; median GI: 48 vs 30.7, p=0.03). No significant differences were observed according to HER2 expression. After PST, 84% of pts was classified as having a TRG 4 or 5, and 16% as having a TRG 1–3. No significant correlation among baseline Ki-67, AI and GI and TRG was observed. After PST, Ki 67 and AI were significantly reduced from baseline. Lower Ki 67 and lower AI were significantly correlated with higher TRG (p=0.008 and 0.01 respectively). We observed 1 cancer death and 5 relapses only, therefore correlation with patient outcome has been planned for the time of the meeting Conclusions: ER- and EGFR+ tumors show more aggressive behaviour. PST significantly reduces Ki-67 and AI, and this reduction is significantly correlated with TRG. In particular, the reduced AI at surgery was not found to be a marker of resistance, more probably reflecting the reduced Ki-67 of responding tumors. No significant financial relationships to disclose.
A phase III comparative study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus everolimus in patients (pts) with advanced or metastatic renal cell carcinoma (mRCC) previously treated with antiangiogenic therapy.
Authors: Robert John Motzer, Petri Bono, Gary R. Hudes, Yoshihiko Tomita, Alain Ravaud, Ian Waxman, Martin Eric Gore
Journal: Journal of Clinical Oncology (2013)

TPS4592 Background: Standard approved treatments for pts with mRCC include interleukin-2 as well as therapies that target the vascular endothelial growth factor (eg, sunitinib, pazopanib) or mammalian target of rapamycin (eg, temsirolimus, everolimus) pathways. However, most pts may develop resistance, and overall survival (OS) improvement has only been shown in one phase 3 trial in poor-risk pts. Everolimus demonstrated a 3-month improvement in median progression-free survival (PFS) vs placebo, with no OS improvement (Motzer RJ, et al. Lancet. 2008;372:449-56). A phase 1 study of the fully human programmed death-1 (PD-1) receptor blocking monoclonal antibody nivolumab showed encouraging antitumor activity with previously treated mRCC (objective response rate [ORR], 29% (10/34); stable disease at ≥24 weeks [wks], 27% [9/34]). PD-1 is an immune checkpoint receptor that negatively regulates T-cell activation and PD-1 overexpression by tumor infiltrating lymphocytes has been associated with poor prognosis in multiple tumor types. Therefore, an ongoing, randomized, open-label, global phase 3 trial was developed to evaluate the clinical benefit of nivolumab in mRCC pts previously treated with anti-angiogenic therapy. Methods: Approximately 822 pts with advanced or metastatic clear-cell mRCC who have received ≤2 prior anti-angiogenic therapies and ≤3 total prior systemic regimens will be randomized 1:1 to receive nivolumab 3 mg/kg IV every 2 wks (Arm A) or everolimus 10 mg PO daily (Arm B). Pts will be stratified by region, MSKCC risk group, and number of prior anti-angiogenic therapy regimens. Tumor response will be assessed using RECIST 1.1 every 8 wks following randomization for the first year and then every 12 wks until disease progression or treatment discontinuation, whichever occurs later. The primary endpoint is OS. Secondary endpoints include PFS, ORR, OR duration, adverse events, OS in PD ligand 1 (PD-L1) positive or negative subgroups, and patient-reported outcomes. The trial is open and enrolling pts. Clinical trial information: NCT01668784.
Mating motives are neither necessary nor sufficient to create the beauty premium
Authors: Sebastian Hafenbrädl, Jason Dana
Journal: Behavioral and Brain Sciences (2017)

Abstract Mating motives lead decision makers to favor attractive people, but this favoritism is not sufficient to create a beauty premium in competitive settings. Further, economic approaches to discrimination, when correctly characterized, could neatly accommodate the experimental and field evidence of a beauty premium. Connecting labor economics and evolutionary psychology is laudable, but mating motives do not explain the beauty premium.