tbuckley/cabot-search huggingface dataset:
Malignant hemangiopericytoma: Treatment patterns and survival.
Authors: Rolando Barjas, David Eric Piccioni
Journal: Journal of Clinical Oncology (2017)

e13520 Background: Hemangiopericytoma (HPC), or solitary fibrous tumor of the central nervous system (CNS), is a rare mesenchymal tumor that arises from the pericytes of the meningeal capillaries. These tumors account for less than 1% of all CNS tumors and are categorized into low-grade (WHO grade I and II) or high-grade (WHO grade III, anaplastic) neoplasms. The optimal treatment for grade III HPC is unclear. The aim of this study was to evaluate treatment patterns and survival for grade III HPC using the California Cancer Registry (CCR). Methods: Treatment and demographic data were extracted from the CCR for patients with grade III HPC of the CNS, from 1988-2010. Overall Survival (OS) was evaluated as a function of treatment (surgery, radiation or both), as well as extent of resection. Kaplan Meier survival analyses were performed for OS. Bivariate and multivariable analyses were done via cox proportional hazard regression models for all demographic and treatment variables. Results: A total of 94 patients with grade III HPC were identified from the registry. The most prevalent demographics were age &gt; 50 years (59%), female (61%), non-Hispanic White (60%), and married (54%). 54% received radiation, and subtotal resection (STR) (63%) was the most common surgical outcome. However, survival was greatest in patients that received gross total resection (GTR) with radiation (median OS not reached). GTR/radiation (median OS not reached) demonstrated improved OS compared to STR/radiation (median OS 10.3 years; HR = 0.389, 95%CI 0.157-0.960) or GTR alone (median OS 6.6 years; HR = 0.254, 95%CI 0.073-0.880). Age &lt; 50 (median OS 15.7 years), Asian/PI (median OS not reached) and married (median OS 9.9 years) were significant predictors of OS. In the multivariable cox model worse overall survival remained for older age (HR = 3.079, 95%CI 1.428-6.636) and divorced/widowed/separated (HR = 2.027, 95%CI 1.054-3.897) when compared to their younger and married counterparts. Conclusions: Patients that received GTR and radiation demonstrated the best long-term prognosis. Demographic analyses identified additional independent predictors of survival.
Sebum lipids influence macrophage polarization and activation
Authors: M. Lovászi, M. Mattii, K. Eyerich, A. Gácsi, E. Csányi, D. Kovács, R. Rühl, A. Szegedi, L. Kemény, M. Ståhle, C.C. Zouboulis, S. Eyerich, D. Törőcsik
Journal: British Journal of Dermatology (2017)

As lipids are known to regulate macrophage functions, it is reasonable to suppose that a sebocyte-macrophage axis mediated by sebum lipids may exist.To investigate if sebocytes could contribute to the differentiation, polarization and function of macrophages with their secreted lipids.Oil Red O lipid staining and Raman spectroscopy were used to assess the dermal lipid content and penetration. Immunohistochemistry was used to analyse the macrophage subsets. Human peripheral blood monocytes were differentiated in the presence of either supernatant from human SZ95 sebocytes or major sebum lipid components and activated with Propionibacterium acnes. Macrophage surface markers and their capacity to uptake fluorescein isothiocyanate-conjugated P. acnes were detected by fluorescence-activated cell sorting measurements. Cytokine protein levels were evaluated by enzyme-linked immunosorbent assay and Western blot analysis.Sebaceous gland-rich skin had an increased dermal lipid content vs. sebaceous gland-poor skin to which all the tested sebum component lipids could contribute by penetrating the dermoepidermal barrier. Of the lipids, oleic acid and linoleic acid promoted monocyte differentiation into alternatively activated macrophages. Moreover, linoleic acid also had an anti-inflammatory effect in P. acnes-activated macrophages, inhibiting the secretion of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α. Squalene, palmitic acid, stearic acid and oleic acid augmented the secretion of IL-1β, even in the absence of P. acnes, whereas oleic acid had a selective effect of inducing IL-1β but downregulating IL-6 and TNF-α secretion.Our results suggest a role for sebaceous glands in modulating innate immune responses via their secreted lipids that are of possible pathological and therapeutic relevance.
Genetic causes of resistance to entinostat in luminal breast cancer model systems.
Authors: Maki Tanioka, Joe Garay, Cheng Fan, Lisa A. Carey, Charles M. Perou
Journal: Journal of Clinical Oncology (2017)

1065 Background: Based on promising phase II data, the histone deacetylase inhibitor Entinostat (ENT) is in phase III trials for patients with metastatic ER-positive breast cancer. Predictors of sensitivity and resistance, however, remain unknown. Methods: Luminal cell lines SKBR3 (ER-/HER2+), BT474 (ER+/HER2+) and MCF7 (ER+/HER2-) were treated with or without ENT at their IC50 doses and their gene expression profiles determined. In addition, a total of 27 MMTV-Neu mouse tumors (luminal) were untreated (N = 8), or treated with ENT at 12 mg/kg for 3 weeks (N = 5), 6 weeks (N = 6), or until progression after complete response (N = 8). We investigated their gene expression profiles by microarray and copy number (CN) by arrayCGH, and utilized the Dawnrank analysis, a network-based bioinformatics tool that integrates DNA and RNA data to identify driver genes, to find predictors of resistance to ENT. Results: Supervised analysis of gene expression data coming from the 3 treated cell lines showed significant upregulation of multiple MYC gene signatures. Therefore, we constitutively overexpressed MYC using lentiviral MYC shRNA in SKBR3 and MCF7, and MYC overexpression made cell lines more resistant to ENT. In MMTV-Neu mice, both MYC gene mRNA and gene signatures were downregulated while cells responded to ENT, and became upregulated when the tumors progressed. aCGH CN analysis revealed that a large portion of mouse Chromosome 4 had DNA CN loss and low gene expression in tumors that progressed while on ENT. Within this region, JUN was computationally identified to be a top driver gene associated with resistance. JUN was next knocked down using lentiviral JUN shRNA in BT474 and T47D, and JUN knock-down repeatedly made cell lines more resistant to ENT. MYC gene-expression was also upregulated in JUN-knockdown BT474 and T47D. Finally, JUN CN loss was found in 22% (132/588) of luminal tumors in The Genome Cancer Atlas breast cancer, and all the MYC signature scores were significantly higher in JUN-deleted TCGA samples. Conclusions: ENT was an effective drug for all of our luminal models, both in vitro and in vivo. Using these models, we selected for resistant variants and identified MYC signature expression, and JUN CN deletion as being associated with resistance.
Evaluation of real-world electronic medical record (EMR) treatment outcome data compared to clinical trial data for an advanced breast cancer treatment.
Authors: Bruce A. Feinberg, Jonathan K Kish, David Garofalo, Urvi Mujumdar
Journal: Journal of Clinical Oncology (2016)

e12506 Background: With increasing interest in value based care multiple value calculators have been introduced that rely on clinical trial efficacy and toxicity data as inputs. However, clinical trial patient mix and outcomes may vary from those patients treated in the community oncology setting. When sufficient time has elapsed since approval, real-world studies of patient populations may be needed to augment trial data for realistic value assessment. Methods: A chemotherapeutic drug approved in 2007 for metastatic/locally advanced breast cancer was examined through a community oncology specific EMR database. Patients with a confirmed diagnosis of advanced breast cancer (N = 199), treated with the drug of interest that conformed to the labeled indication, during the period (December 2007 –November 2015) and with at least 6 months of continuous follow up were included in the study. Patients with treatment for a secondary cancer or participation in any clinical trial were excluded. Progression free survival (PFS) was defined by time from drug initiation to either initiation of a subsequent line of therapy (LOT), discontinuation of therapy (no subsequent LOT), or death from any cause. Results were compared against package insert referenced clinical trial data. Results: The pivotal clinical trial data consisted of patients (N = 375) that were 67% white, median age 53, baseline Karnofsky 70-100%. Median PFS was 5.7 months. Patients identified through EMR data were 45% white (although 30% unknown race), median age 58, baseline ECOG performance status of 1.2 (available for 47% of patients). Median PFS of 4.3 months (95% confidence interval, 3.9–5.5). Conclusions: This real-world EMR data analysis affirms prior reports with patients older, sicker, and possibly less diverse than their trial cohort. A 25% shorter PFS is a significant finding that may impact on value calculation. Further study is needed to compare real world patient populations to clinical trial populations and account for differences in demographics and expected treatment outcomes, especially given that clinical trial data is informing newly developed value calculators.
Comparison of four cycles epirubicin and cyclophosphamide (EC) followed by four cycles docetaxel (T) versus six cycles docetaxel and carboplatin (TP) as adjuvant chemotherapy for women with operable triple negative breast cancer.
Authors: Peng Yuan, Feng Du, Jiayu Wang, Fei Ma, Ying Fan, Binghe Xu
Journal: Journal of Clinical Oncology (2016)

1068 Background: To determine optimal adjuvant chemotherapy for early triple negative breast cancer depends on efficacy and toxicity. We sought to examine if six cycles TP is non-inferior to standard four cylces EC followed by four cycles T but with shorter treatment duration and reduced toxicity. Methods: Pts with operable triple negative breast cancer were enrolled and randomized (1:1) to receive either six cycles TP (docetaxel:75 mg/m2; carboplatin: AUC = 5, day 1) or four cycles EC(epirubicin: 90 mg/m2; cyclophosphamide :600mg/m2 , day 1) followed by four cycles T (docetaxel : 100mg/m2 , day 1). Both regimens were repeated every three weeks. Randomization was stratified by lymph node status. The primary end point was median DFS. A sample size of 500 patients were required to detect the difference (a = 0.05, β = 80%). Results: From June 2010 to Jan 2015, 298 pts were enrolled in the study including 152 pts in EC-T arm and 146 pts in ET arm. Patients' characteristics were well balanced between two arms. In total, 60.5% and 69.9% of patients were node-negative in EC-T arm and TP arm, respectively. In addition, the proportion of patients diagnosed as TNM Stage I, II and III was 33.6%, 55.3% and 11.2% in EC-T arm, whereas it accounted for 39.0%, 54.1% and 6.2% in TP arm. After median 39.5 months followed-up, 32 events were observed (16 in EC-T, 16 in TP). The 5y DFS was 83.8% in EC-T arm and 80.0% in TP arm (log-rank p = 0.961, HR 0.983, 95%CI = 0.490—1.970). Both regimens were well tolerated. The most frequent hematological toxicity was neutropenia (Grade 3/4: 67.8% in EC-T vs. 39.0% in EP). The most frequent non- hematological toxicity were anorexia (All Grades: 80.3% in EC-T vs. 62.3% in EP), liver dysfunction (All Grades: 32.2% in EC-T vs. 24.0% in EP), and neurosensory difficulties (All Grades: 26.3% in EC-T vs. 15.8% in TP). Conclusions: Benefit from six cycles TP was similar as from four cycles EC followed by four cycles T, with lower toxicity observed in patients with operable triple negative breast cancer. Clinical trial information: NCT01150513.
Bioinformatic analysis of the colonic polyp-cancer pathway
Authors: AC Moss, D Sadleir, P Doran, J Leyden, C O'Keane, P MacMathuna
Journal: Endoscopy (2005)

Background: The pathways implicated in progression from normal colonic mucosa to polyps to cancer are not fully elucidated. Examination of transcribed genes at each step of progression may identify markers of disease progression.
The impact of single and multiagent chemotherapy on stage III colon cancer survival.
Authors: Aabra Ahmed, Ahmed I Tahseen, Katrina Wolfe, Ryan W Walters, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2016)

e13093 Background: NCCN guidelines recommend Folfox chemotherapy for patients under age 70, but state that there is no clear benefit of oxaliplatin in adjuvant therapy for stage III colon cancer for patients over the age of 70. Methods: We examined 55,855 elderly patients and 70,416 patients under age 70 to determine the difference in survival between those with single or multiagent chemotherapy versus no chemotherapy by examining the National Cancer Database (NCDB), which includes 70% of all newly diagnosed cancer patients. As Folfox is the only FDA approved multiagent chemotherapy, we assume that this was the treatment given. Kaplan Meier analysis was conducted to analyze survival. Charlson Deyo (CD) scores, which quantitated the number of comorbidities from 0-2, were examined. Chi-square analysis was done to determine significance of survival differences between treatment groups. Results: Patients under age 70 had approximately doubled median survival when given single agent chemotherapy, whereas patients over 70 had tripled median survival as compared to not receiving chemotherapy. Relative to single agent chemotherapy, multiagent chemotherapy provided no more than a 12.4% increase in survival. Multiagent chemotherapy use decreased as age increased, but single agent chemotherapy use slightly increased. CD scores did not differ greatly between those with and without chemotherapy within age groups. Conclusions: This is the largest study to evaluate the use of adjuvant chemotherapy in stage III colon cancer patients. We found that in all age groups, single agent chemotherapy provided 2-3 fold improvement in survival as compared to no chemotherapy. The incremental advantage of multiagent chemotherapy was less than 13% in all age groups, and was associated with a decrease in survival for patients over age 80. Summary of data. Under 70 70-74 75-79 80+ Survival No chemo (mo.) 64 27 24 19 Survival Single Agent (mo.) 121 87 73 54 Survival Multiagent (mo.) 127* 98* 78* 51* CD No chemo 0.33 0.52 0.53 0.50 CD Single Agent 0.35 0.48 0.47 0.40 CD Multiagent 0.26 0.39 0.39 0.36 % No chemo 11 18 25 62 % Single Agent 12 19 27 21 % Multiagent 77 62 47 16 *p < 0.05 between no, single, multiagent chemo
Correlation between HER2 related biomarkers (HER2, p95HER2, HER3, PTEN and PIK3CA) and treatment outcome of lapatinib plus capecitabine in HER2-positive metastatic breast cancer refractory to trastuzumab.
Authors: Reiki Nishimura, Uhi Toh, Maki Tanaka, Michiyo Saimura, Yasuhiro Okumura, Tsuyoshi Saito, Toshihiro Tanaka, Megumi Teraoka, Kazuo Shimada, Kazuhisa Katayama, Toshihiro Koga, Kaname Kurashita, Satoshi Hasegawa, Hidekazu Todoroki, Hiroaki Ueo, Nobuyuki Arima, Shoshu Mitsuyama, Kazuo Tamura
Journal: Journal of Clinical Oncology (2016)

e12085Background: Trastuzumab (Tmab) has contributed to improving the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, some cases did not respond or wer...
Quantitative Baseline Circulating Tumor DNA Levels Correlate with GM-CSF Response to Idiotype Vaccine in Untreated Mantle Cell Lymphoma
Authors: Mark Roschewski, Kieron Dunleavy, Sattva S. Neelapu, Stefania Pittaluga, Christopher Joseph Melani, Elaine S. Jaffe, Margaret Shovlin, Beryl Crossley, Katie Kong, Allison Jacob, Larry Kwak, Wyndham H. Wilson
Journal: Blood (2016)
ALK and EGFR mutation analysis in a phase II trial of cisplatin/pemetrexed in Japanese patients with advanced nonsquamous non-small cell lung cancer.
Authors: Kyohei Kaburaki, Fumiyoshi Ohyanagi, Azusa Tanimoto, Toshio Sakatani, Yuko Kawano, Ryota Saito, Noriko Yanagitani, Keita Kudo, Atsushi Horiike, Sachiko Hagiwara, Noriko Motoi, Kengo Takeuchi, Yuichi Ishikawa, Takeshi Horai, Makoto Nishio
Journal: Journal of Clinical Oncology (2012)

e18017 Background: Recently, ethnic differences and genotypes such as EGFR mutation (EGFRm) or fusion gene (ALK translocation: ALKt) are important factors in non-small cell lung cancer (NSCLC) treatment. Pemetrexed (P)/cisplatin (C) is one of the standard care for advanced non-squamous (Nsq) NSCLC. However, the efficacy of the CP regimen has not been well examined in Japanese Nsq NSCLC patients (pts); furthermore, the difference in efficacy between genotypes was not thoroughly examined. Therefore, the present study was conducted to evaluate the efficacy of the CP regimen in Japanese Nsq NSCLC pts, and to determine whether EGFRm and ALKt impacted the treatment. Methods: This study was conducted from May 2009 to December 2010. Pts were eligible for this study if they had histologically or cytologically confirmed recurrent or metastatic Nsq NSCLC previously untreated with chemotherapy, an ECOG performance status of 0 or 1, life expectancy of more than 12 weeks, and adequate organ function. Pts received C (75 mg/m 2 ) plus P (500 mg/m 2 ) on day 1 every 3 weeks. Of the 50 pts initially enrolled, 49 were evaluated, and 43 tumor samples were available for analysis. Most pts were male (80%), and 80% of the pts had adenocarcinoma. The primary endpoint was the response rate that was evaluated according to RECIST. EGFRm was examined using PCR-based methods, and the ALK fusion protein was examined using a highly sensitive IHC method in the available tumor specimens. Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment. Results: The objective response rate and disease control rate in all pts were 44.9% and 79.6%, respectively. The median progression-free survival was 4.4 months, and the 1-year survival was 73.5%. Toxicities were mild; no new toxicity profile was identified. Among the 43 samples, the following mutations were identified: 9 EGFRm (21%), 5 ALKt (12%), and 29 wild-type (67%). Objective response was observed in 6 (66.7%) EGFRm, 2 (40%) ALKt, and 13 (44.8%) wild-type. Conclusions: Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment.
A phase I study of LY3022855, a colony-stimulating factor-1 receptor (CSF-1R) inhibitor, in patients (pts) with advanced solid tumors.
Authors: Afshin Dowlati, Hope S. Rugo, R Donald Harvey, Ragini Reiney Kudchadkar, Richard D. Carvajal, Gulam Abbas Manji, Omid Hamid, Samuel Jacob Klempner, Shande Tang, Danni Yu, John S. Kauh, David Arlen Schaer, Sonya Catherine Tate, Robert Wesolowski
Journal: Journal of Clinical Oncology (2017)

2523 Background: Binding of CSF-1 to the CSF-1 receptor (CSF-1R) results in proliferation, differentiation, and migration of monocytes/macrophages. Intratumoral infiltration with macrophages correlates with increased invasiveness, growth, and immunosuppression. LY3022855 (LY) is a human IgG1 antibody (mAb) targeting CSF-1R. Methods: Eligible pts (ECOG 0-2) with advanced solid tumors were enrolled. Mandatory pre and post-treatment biopsies were obtained. LY was given on a 6-week cycle. Two escalation regimens (Part A: weight-based dosing; Part B: flat dosing) were investigated in a 3+3 design. Primary objective was to establish the safety and characterize the pharmacokinetics (PK) of LY. Secondary objectives were to establish recommended phase 2 dose (RP2D) and to characterize pharmacodynamics (PD). Results: As of Sept 6, 2016, 35 cancer pts (colorectal 14; lung 4; pancreas 3; others 14) were treated (29 in Part A; 6 in Part B) with median treatment duration 4 weeks (range 1-21). Common treatment-emergent adverse events (TEAEs) were fatigue (54%), hypoalbuminemia (40%), nausea (37%), AST increase (37%), anemia (34%), anorexia (34%), creatine kinase elevation (29%), and constipation (23%). Most common grade (G) 3/4 TEAEs were anemia (11%), fatigue (11%), ascites (9%), and lymphocyte count decrease (9%). 3/28 evaluable pts had DLTs: G3 left ventricular systolic dysfunction (1), G4 rhabdomyolysis and G4 acute renal failure (1), and G3 pancreatitis (1). Eight treatment unrelated deaths were reported. One pt (adenoid cystic carcinoma) had stable disease (~3 mo as of last visit), 19 pts had progressive disease, and 15 pts were non-evaluable for response assessment. PK profile of LY was consistent with IgG1 mAbs. An interim analysis following completion of Part A demonstrated a lack of relationship between weight and clearance, prompting evaluation of non-weight based dosing. PD analyses revealed dose-dependent increases in serum CSF-1 levels as well as suppression of circulating non-classical monocytes (CD14 dim CD16 bright ), indicating biologic activity at studied doses. Conclusions: RP2D for LY monotherapy has been determined. Detailed PK and PD data will be presented. Clinical trial information: NCT01346358.
Attitudes of patients and physicians to repeat biopsies for lung cancer.
Authors: Puey Ling Chia, Paul Mitchell, Thomas John
Journal: Journal of Clinical Oncology (2016)

e18221 Background: As targetable resistance mutations and other molecular drivers are discovered in lung cancer, increasingly repeat biopsies are suggested both in the clinical and research context. However patient and clinician attitudes towards repeat invasive procedures may be discordant. We conducted a prospective patient and physician survey to investigate patient’s and physician’s attitudes towards repeat biopsies in lung cancer. Methods: Under an ethics approved protocol, patients attending the lung oncology clinic at a large academic centre in Melbourne were invited to complete a questionnaire assessing their attitudes on repeat biopsies. Physicians and surgeons who treat lung cancer patients were invited to complete an online questionnaire through the Australasian Lung Cancer Trials Group (ALTG). Results: 87 respondents completed their respective questionnaires. There were 48 patients [Male: Female ratio 1:1, median age 68 years, metastatic (60%): locally advanced/adjuvant (40%)] and 39 physicians. The most important factor in a patient’s decision to undergo repeat biopsy was their oncologist’s recommendation (57%). Most physicians (75%) were willing to accept up to 20% risk of complications. The majority (92%) of physicians supported rebiopsy to identify biomarkers that would alter treatment strategies, whereas only 53% would recommend research-only biopsies (which did not have direct impact on management). Similarly, the majority of patients would agree to a repeat biopsy in order to participate in a clinical trial (63%) or on progression of disease to check on the resistance mechanism (68%), however, when patients were asked to consider a biopsy for the sole purpose of research, acceptance fell to 50%. Most respondents felt that a wait time of up to 14 days for molecular analysis was acceptable. Conclusions: The decision by lung cancer patients to undergo rebiopsy was strongly influenced by their oncologists’ recommendations. Most would agree to a repeat biopsy in order to participate in a clinical trial or on progression of disease to check on the resistance mechanism. However, only 50% of patients and clinicians were interested in repeat biopsies solely for research purposes.
Le drainage sous échoendoscopie des pseudokystes pancréatiques est-il toujours inidspensable?
Authors: M Barthet, B Madougou, M El Farisi, M Gasmi, A Desjeux, JC Grimaud
Journal: Endoscopy (2006)

Le traitement endoscopique des kystes et pseudokystes pancréatiques (PK) est devenu un traitement de première intention. L'absence de bombement digestif ou de communication peut empêcher un drainage endoscopique transmural ou transpapillaire. L'échoendoscopie en peut théoriquement augmenter la faisabilité et diminuer la morbidité du traitement endoscopique.