tbuckley/cabot-search huggingface dataset:
The role of adhesion molecules in hepatocellulary carcinoma.
Authors: Didem Tastekin, Mustafa Dikilitas, Hakan Harputluoglu, Kayhan Ertürk, Koray Celebi, Fatma Sen, Hamza Ugur Bozbey, Nakiye ÃÂ¶ZtÃÂ¼rk
Journal: Journal of Clinical Oncology (2015)

e15144 Background: Hepatocellulary carcinoma (HCC) consists of 85-90 % of liver tumors.. Several molecular markers are developed for early diagnosis. Adhesion molecules like VCAM and EPCAM are in these group. Adhesion molecules take part in regulation of different functions such as tropism of cells to spesific tissues, identify each other, embryogenesis, cell growth and differentiation and inflammation. Vascular cell adhesion molecule-1 (VCAM-1) interferes with integrins in VLA group, found in leucocytes. These molecules are expressed in endothelial cells, antigen presenting cells, bone marrow stromal cells, embrionic and synovial tissue. Epithelial cell adhesion molecule (EpCAM) is a 40 kDa weisght cell surface antigen. As expression of EpCAM is increased in tumour cells it is ssuggested that this molecule can be predictive marker for malignancy. Methods: This study was conducted to determine serum levels of VCAM and EPCAM which may have diagnostic or prognostic value in blood samples of patients with HCC.Sixty newly diagnosed HCC patients and 20 healthy subjects admitted to Istanbul University Institute of Oncology and department of gastroenterohepatology were included in the study. Serum levels of VCAM and EPCAM were analysed in duplicated manner by ELISa assay. SPSS 16 sofware programme was used for stastical analyses. Results: There was a stastically significant difference between patient and control groups in respect to VCAM and EPCAM levels (p < 0.001) Conclusions: Our results suggested that adhesion molecules may be useful in early diagnosis of HCC. When one year survival data were evaluated it seems that VCAM and EPCAM have no prognostic value.
Prognostic and predictive significance of smudge cell percentage on routine blood smear in chronic lymphocytic leukemia patients: A single center study from northern India.
Authors: Ajay Gogia, Vinod Raina, Atul Sharma, Lalit Kumar, Ritu Gupta, Sreeniwas Vishnubhatla, Smeeta Gajendra
Journal: Journal of Clinical Oncology (2012)

6593 Background: Smudge cells are ruptured lymphocytes seen on routine blood smears of chronic lymphocytic leukemia (CLL) patients. We evaluated prognostic and predictive significance of smudge cells percentage on a blood smear in CLL patients. Methods: We calculated smudge cell percentages (ratio of smudged to intact cells plus smudged lymphocyte) on archived blood smears of 185 untreated CLL patients registered at I.R.C.H, AIIMS, New Delhi over a period of 11 years. Results: There were 135 males and 50 females. The median age was 60 years (28-89). Median absolute lymphocyte count was 42 X10 9 /L. Clinical Rai stage distribution was: stage 0 - 10%, stage I - 15%, stage II - 40%, stage III -15 % and stage IV - 20%. The median smudge cells percentage was 27% (4% to 76%). There was no correlation of proportion of smudge cells with age, sex, lymphocyte count, organomegaly, ZAP 70 + or CD 38 + CLL patients, but there was significant correlation with stage of disease. Median smudge cell percentage in stage 0 &amp; I -33% (12-76), stage II- 31% (12-61) and stage III&amp;IV-21% (4-51) [ p=&lt;0.001]. One third of early stage (0, I &amp;II) patients required treatment during follow up, at the end of 5 years of follow up 55% required treatment with smudge cell &lt; 30%, against 24% patients requiring treatment with smudge cells &gt; 30% [p=0.01]. The percentage of smudge cells as a continuous variable correlated with OS [HR 0.96, p&lt; 0.001]. The 5-year survival rate was 51% for patients with 30% or less smudge cells compared with 81% for patients with more than 30% of smudge cells. Thirty percent of patients died during follow up. Median OS was 5 years with median follow up period of 3.9 years. Smudge cells percentage (&lt;30% vs. &gt;30%) had significant association with OS [HR 0.47, 95%CI (0.32-0.71), p=0.001)]. Conclusions: Simple and inexpensive detection of smudge cells on blood smears on routine diagnostic test useful in predicting progression free and OS in CLL patients and may be beneficial in countries with limited recourses.
Everolimus in metastatic breast cancer (MBC): Clinical experience as a late treatment line.
Authors: Mélanie Pouget, Catherine Abrial, Eloise Planchat, Isabelle Van Praagh, Marie Arbre, Fabrice Kwiatkowski, Pascale Dubray-Longeras, Herve Devaud, Qian Wang-Lopez, Hakim Mahammedi, Xavier Durando, Philippe J. M. Chollet, Marie-Ange Mouret-Reynier
Journal: Journal of Clinical Oncology (2015)

e11526 Background: Everolimus, in combination with exemestane, is indicated to treat hormone receptor-positive, HER2-negative metastatic breast cancer (MBC), in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor. However, efficacy of everolimus as a late treatment line in MBC has not been sufficiently explored. We report here our experience with everolimus in patients (pts) pretreated by a median of 3 chemotherapy (CT) and 2 hormonotherapy (HT) lines in the metastatic setting. Methods: Between 2012 and 2014, 63 MBC pts progressing under HT (30 pts) or after CT (32 pts) received a combination of everolimus and HT (EHT) for a median duration of 27.8 weeks. Overall survival (OS) was calculated from the onset of EHT, to last report or death. Results: At the cutoff date (February 2014), median OS was not reached after a median follow up of 18 months;18 patients had died. At 12 months, the survival rates were respectively 100, 79 and 49 % for pts pretreated by 0 (13 pts), 1-2 (18 pts), ≥ 3 (32 pts) CT lines in the metastatic setting Pts with previous two lines of CT or less (31 pts) had a better survival rate than those with > 2 lines (32 pts) (p = 0.016). Pts who received two lines of HT or less (38 pts) tended to have better survival vspts with > 2 lines (25 pts) (p = 0.083). Pts with stomatitis (36 pts) tended to have better survival than pts without stomatitis (26 pts) (p = 0.11). OS was similar according to the presence of visceral (p = 0.40), or bone metastasis (p = 0.72) or with patient weight (p = 0.74). The number of previous CT lines and triglyceridemia (TG) were significantly correlated to OS in univariate analysis (UA) (p = 0.016 and p = 0.0074 respectively). OS decreased for pts with > 2 CT lines and increased for pts with TG > ULN (Upper Limit Normal). All significant factors in UA were included into a multivariate analysis. In the Cox model, TG > ULN was a prognostic factor, determining a longer OS (p = 0.04). Conclusions: These OS and tolerance results may support EHT as a supplementary line, instead of a new CT, especially in pts who had received 2 lines of CT or less. In effect OS was at least widely comparable to our published series (PMID 21852136), even if confirmatory studies are needed.
Inflammatory phenotype of classical (CD14++CD16-) monocytes in patients with advanced non-small cell lung cancer.
Authors: Fiona Margaret McCarthy, Cristina Ghirelli, Raphael Zollinger, Melissa Phillips, Rozita Roshani, Juliana Candido, Roisin Trehy, Michael Sheaff, Jeremy Steele, Thorsten Hagemann
Journal: Journal of Clinical Oncology (2013)

11071 Background: Monocytes are intrinsic members of the innate immune system and play an important role in immunity and inflammation. Human monocytes are subdivided into three populations depending on cell surface CD14 and CD16 expression: Classical (CD14 ++ CD16 - ), intermediate (CD14 + CD16 - ) and non-classical (CD14 - CD16 ++ ). These populations have diverse functions and have been postulated to play both anti and pro-inflammatory roles in a variety of diseases including atherosclerosis, sarcoidosis and other rheumatological conditions. However, the prevalent monocyte populations in cancer have not as yet been identified. We aim to define the prevalent monocyte populations in non-small cell lung cancer as well as further characterising them using flow cytometry and Affymetrix technology. Methods: Blood was obtained from 24 newly diagnosed patients with advanced non-small cell lung cancer and 12 age matched healthy donors. Monocyte subpopulations were sorted using flow cytometry. Gene expression profiling was performed using Affymetrix Human U133 Plus 2.0 array. Results: The classical (CD14 ++ CD16 - ) monocyte population is significantly increased in non-small cell lung cancer patients when compared to healthy donors (p&lt;0.01). The intermediate (CD14 + CD16 + ) and non-classical (CD14 - CD16 ++ ) populations are unchanged. Analysis of the gene expression profile of the classical monocyte subset identified 265 up-regulated and 261 down-regulated genes in cancer patients compared to healthy donors (p&lt;0.05, fold change &gt;2). These genes were assigned to biological processes with gene ontology annotation. Functional annotation reveals a strong association of regulated genes with the G.O term “inflammation” (p=0.009). Among these inflammatory genes are a cluster of chemokines including CXCL2 and CXCR4. Conclusions: By identifying the prevalent monocyte subsets as well as characterising their function in cancer, there is the potential to target detrimental effects and promote their beneficial functions. As such, monocytes subsets may be used as a possible therapeutic target.
CLOVIZ: Clinical outcomes visualization of IMDC criteria in metastatic renal cell carcinoma for patient-centered decision making.
Authors: Anobel Y. Odisho, Sumanta K. Pal, Michael Shapiro, Ashley Dixon, Connor Wells, Jose Manuel Ruiz Morales, Toni K. Choueiri, Daniel Yick Chin Heng, John L. Gore
Journal: Journal of Clinical Oncology (2017)

527 Background: The International Metastatic Renal Cell Carcinoma Database (IMDC) Criteria (Heng Criteria) is a validated risk prediction tool for patients with metastatic renal cell carcinoma (mRCC). It provides valuable prognostic data but clinical application can be challenging due to limited available tools. We created an interactive visualization to facilitate clinical application of IMDC Criteria. Methods: A multi-institutional cohort of 436 patients with mRCC was used to create an interactive visualization depicting IMDC Criteria at the patient level. Usability testing was performed with non-medical lay-users and medical oncology fellows. Subjects used the tool to calculate median survival times based on IMDC Criteria in six increasingly complex clinical scenarios. Confidence using the tool was surveyed and measured along a 5-point Likert scale. Results: The interactive visualization is available at http://faculty.washington.edu/odisho . 400 lay-users and 15 medical oncology fellows completed clinical scenarios and surveys. Overall, lay-users were able to obtain the exact correct answer in 48% of scenarios, compared to 60% of medical oncology fellows. The proportion of exact correct answers decreased with increasing task complexity, but the proportion of answers within 25% of the expected answer remained stable at 68-78% for lay-users and 73-93% for medical oncology fellows. When surveying usability, 65% of lay-users felt it was easy to use, compared to 80% of fellows, and 83%-87% felt it became intuitive with increasing use. Among lay-users, 69-77% were confident selecting lab values and drugs, compared to 87-93% of medical oncology fellows. 75% of lay-users felt it helped them better understand survival in mRCC. 68% of lay-users wanted to use a similar tool with their doctor, while 87% of medical oncologists wanted to use this with patients, and 93% wanted to incorporate it into their clinical practice in some way. Conclusions: A graphical method of interacting with a validated nomogram for mRCC outcomes provides real-time individual level data that can be used by untrained nonmedical users and medical oncologists, with potential for use in the clinic setting.
Meta-analysis to determine the clinical effectiveness of axillary lymph node dissection in the treatment of operable primary breast cancer.
Authors: Doireann Joyce, Aidan Manning, Arnold D. Hill, Malcolm R. Kell, Mitchel Barry
Journal: Journal of Clinical Oncology (2013)

1112 Background: The optimum surgical management of the axilla is controversial. Guidelines mandate axillary surgery in the setting of positive sentinel nodes. However, recent studies have questioned the oncological benefits of this potentially morbid procedure. Therefore a meta-analysis of relevant randomised trials was performed to clarify this issue. Methods: A comprehensive search of published randomized trials that compared patients with primary operable breast cancer with/without axillary lymph node dissection (ALND) was performed using MEDLINE and available data was cross referenced. Reviews of each study were conducted, and data were extracted. Primary outcomes were overall survival and recurrent axillary disease. Results: A total of 4,759 patients with operable primary breast cancer were identified from 13 randomised controlled trials comparing patients with/without ALND. Overall survival favours patients not having ALND (OR = 1.38 (95% CI = 1.12 TO 1.69, p=0.002)) however patients undergoing ALND had similar disease free survival (OR=1.04 (95% CI= 083-1.31, p=0.7). However, though axillary recurrence was uncommon it was significantly less so following ALND (1% vs. 5 %, p&lt;0.05, ALND vs. No ALND). Conclusions: Based on this meta-analysis, ALND does not appear to positively impact on breast cancer survival. Enhanced and targeted adjuvant treatment strategies may facilitate less aggressive axillary surgery. The management and implications of a positive sentinel node need to be re-evaluated in this regard.
Sentinel lymph nodes before chemotherapy: The Besançon experience.
Authors: Loic Chaigneau, Elsa gannard Pechin, Hamidi Almotlac, Guillaume Mouillet, Fernando Bazan, Cristian Villanueva, Laurent Cals, Philippe Montcuquet, Nathalie Meneveau, Thierry Nguyen, Elsa Curtit, Jean-Loup Sautiere, Yolande Maisonnette, Marie-Paule Algros, Xavier B. Pivot
Journal: Journal of Clinical Oncology (2013)

1122 Background: It is debatable whether sentinal lymph node (SLN), before chemotherapy in locally breast cancer (LBC) is feasible. Impact on survival and locoregionally recurrence are unknown. Methods: 256 consecutive patients with LBC treated in Franche Comté (France) between 2004 and 2010 by standard neoadjuvant chemotherapy were retrospectively studied. 177 patients underwent axillary lymph node (ALN) dissection after chemotherapy (cohort A) and 79 patients underwent SLN before chemotherapy (cohort B). The aim of this study was designed to confirm the feasible of SLN before neoadjuvant chemotherapy without negative impact of recurrence and survival. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier method. Differences in OS and DFS according ALN exploration were tested for significance using the Log-Rank test. Results: No statistically significant differences were observed in terms of median age (respectively 59 and 48 years in cohort A and B), tumor size, histological type, grading score, estrogen receptor, progesteron receptor and human epidermal receptor-2 status. No difference of breast conserving surgery was observed between cohort A and B (56.25 vs. 64.56%, p = 0.21). In cohort B, 38 patients (48.10%) of patients underwent SLN alone. For others patients (n = 41, 51.90%), secondary complete axillary lymphadenectomy was performed in the same time of breast surgery. After a median follow up of 57 months (range: 38-105), there was no significant difference in termsof local and axillary recurrences (1.13 vs. 1.27%), metastatic recurrence (11.30 vs. 11.40%). Five-year DFS (76 vs 81%, p = 0.55) and 5-year OS (91 vs. 97%, p = 0.76) did not differ between patients in cohort A and B. Conclusions: SLN before neoadjuvant chemotherapy is feasible and allows to avoid ALN dissection in nearly 50% of patients without impact on recurrence and survival.
Galeterone in men with CRPC: Results in four distinct patient populations from the ARMOR2 study.
Authors: Robert B. Montgomery, Mario A. Eisenberger, Elisabeth I. Heath, A. Oliver Sartor, Franklin Chu, Neal D. Shore, William Jeffery Edenfield, Alan J. Koletsky, David Uri Lipsitz, James S. Cochran, Luke T. Nordquist, Jennifer Roberts, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2014)

5029 Background: Galeterone is a 1st in class oral small molecule that disrupts androgen receptor (AR) signaling via multi-targeted mechanism of action (1) selective inhibition of CYP17 lyase; (2) competitive antagonism of androgen binding to AR; and (3) degrading of AR protein. CYP17 enzyme inhibition (abiraterone) and AR antagonism (enzalutamide) separately have shown significant activity in metastatic castrate resistant prostate cancer (mCRPC) and considered standard treatment for these pts. Galeterone is a single molecule that has the potential advantage to target both mechanisms. Methods: ARMOR2 (NCT# 01709734) is a 2 Pt Phase 2 study designed to confirm dose of reformulated galeterone (spray dry dispersion; SDD) (Pt 1) and assess the safety and efficacy of the dose, 2550 mg QD for 12 wks, in 4 distinct CRPC pt cohorts; non-metastatic tx naïve (M0 TN, n= 7, median PSA=15.6 ng/dL, median PSA DT=2.30 mo), metastatic tx naïve (M1 TN, n=24, median PSA = 22.9 ng/dL, median PSA DT=2.3 mo), abiraterone refractory (Abi-R, n=11, median PSA=35.8 ng/dL, median PSA DT=1.57 mo) and enzalutamide refractory (Enza-R, n=2, median PSA = 72.85 ng/dL, median PSA DT=1.97 mo). This abstract presents interim results of the 2550 mg dose for pts treated in both Pt 1 and 2. Results: Response was seen at 2550 mg in all tx groups, including decreases in PSA. In the most mature dataset of 24 M1 TN pts, PSA decreases of 30% (92%), and 50% (83%) were reached. Data on the M1 group showed encouraging preliminary objective responses (ORR) in 7 of 8 (86%) evaluable pts at 3 months. Safety: Drug was well tolerated by all tx groups. 94% of all adverse events (AE) were gr1 or 2 in severity. Most common < gr 2 AEs were GI (nausea, diarrhea), fatigue and pruritis with no mineralocorticoid excess (ME) or seizures. Conclusions: SDD Galeterone has shown significant biochemical activity and preliminary clinical activity and is well tolerated with no ME or seizures. These data support continued testing of this unique compound in pts with prostate cancer. Clinical trial information: NCT01709734.PSA response by tx group. Tx Group N Pts with >30% n (%) Pts with > 50% n (%) M0 TN 6* 5 (83) 4 (67) M1 TN 24* 22 (92) 20 (83) Abi-R 5** 2 (40) 0 (0) Enza-R 2 NA NA *N= # of pts completing 12 wks, reached PSA 50 or terminated early. **N= # of pts completing 12 wks.
Scrambler therapy for treatment of chemotherapy-induced peripheral neuropathy.
Authors: Breanna L Weisbrod, Deirdre R. Pachman, Drew K. Seisler, Debra L. Barton, Kelliann C. Fee-Schroeder, Thomas J. Smith, Daniel Honore Lachance, Heshan Liu, Andrea L. Cheville, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2014)

9622 Background: More effective treatment is needed for chemotherapy-induced peripheral neuropathy (CIPN). Preliminary data support the use of Scrambler therapy, a device which treats pain via non-invasive cutaneous electrostimulation, for the treatment of CIPN (Smith TJ et al. J Pain Symptom Manage 2010). The current abstract reports data from a pilot trial, performed to investigate the effect of Scrambler therapy for the treatment of established CIPN. Methods: Eligible patients: age ≥ 18 years, ECOG PS ≤2, life expectancy ≥3 months, CIPN symptoms of ≥1 month duration with tingling and/or pain ≥4/10 during the prior week. Patients were treated with Scrambler therapy to the affected area(s) for up to 10 daily 30 minute sessions. Symptoms were monitored using a neuropathy questionnaire consisting of numerical analogue scales ranging from 0-10, daily before therapy as well as weekly for 10 weeks after therapy. Descriptive summary statistics formed the basis of data analysis. During the daily therapy, last values carried forward were used. Results: We report on 37 patients enrolled between 7/18/2011 and 5/6/2013, 12 men and 25 women; the mean age was 58. While the study technically remains open to obtain more experience with this procedure, the first 37 accrued CIPN patients are the basis of our final CIPN-related manuscript from this project (in development). Patients had a history of exposure to various neurotoxic chemotherapeutic agents and the majority (78%) had symptoms ≥1 year. 25 patients were treated primarily on their lower extremities while 12 were treated primarily on their upper extremities. The table portrays data (average symptoms during the previous 24 hours) at baseline, on the last of the 10 planned days of therapy, and at the end of 10 weeks of follow up, regarding patient reported pain, tingling, and numbness. There were no substantial adverse events. Conclusions: Scrambler therapy appears to be effective for the treatment of CIPN: a prospective placebo-controlled clinical trial should be performed. Clinical trial information: NCT01347723. Mean baseline score Mean final Rx score (day 10) Average percent drop in score (day 10) Mean final Rx score (week 10) Average percent drop in score (week 10) Pain 5.8 2.6 53% 3.1 47% Tingling 6.0 3.3 44% 2.9 26% Numbness 6.3 4.0 37% 2.9 46%
Natural history and outcome in a large series of primary dermatofibrosarcoma protuberans (DFSP) treated at a reference institution.
Authors: Andrea Pierluigi Fontana, Chiara Colombo, Marco Fiore, Stefano Radaelli, Silvia Stacchiotti, Vittoria Colia, Paola Collini, Marta Barisella, Gianpaolo Dagrada, Silvana Pilotti, Paolo Giovanni Casali, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2015)

10554 Background: DFSP is a rare sarcoma, characterized by an indolent course, although local recurrences (LR) and occasional distant metastases (DM) are described. We sought to investigate its natural history and prognostic factors in a large series of patients (pts). Methods: All consecutive pts affected by primary DFSP, located at any sites, treated at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, from January 1993 to December 2012, were retrospectively reviewed. Overall Survival (OS), surgical margins status, LR and DM were analyzed. Results: 270 pts were identified, 246 (91.1%) affected by classic (C)-DFSP and 24 (8.9%) by fibrosarcomatous (FS)-DFSP. All pts are alive at a median follow-up (FU) of 6 yrs (range 1-15), save for two of them, dead for other diseases. All pts underwent macroscopic complete surgery. Microscopic margins were negative in 247 cases (91.5%), positive (PM) in 23 (8.5%). Overall, LR occurred in 4 pts (1.5%), 2/21 C-DFSP with PM, 2/2 FS-DFSP with PM, respectively. 3 of the LR were located to the scalp, 1 in the groin. A wider resection was repeated on 3 pts, who are disease-free (DF) after 2, 4 and 8 yrs, respectively. One pt refused surgery, her disease is under control with imatinib (IM) after 3 yrs. DM occurred in 3 pts (1.1% of the whole series; 12.5% of FS-DFSP), all affected by FS-DFSP (2 lung and 1 pancreatic metastases). 2 pts were treated with a lung wedge resection. One was DF after 78 mos, the other recurred again after 14 mos and was further treated with a combination of IM and a second surgery. He is still on IM and DF after 6 mos. The last metastatic pts is also on IM and progression-free after 4 mos. Conclusions: Negative margin resection is always curative for C-DFSP, as the observed metastatic risk is nil. PM may be accepted, when cosmesis is an issue, because LR risk remains low and salvaged by a subsequent wider resection. FS-DFSP has a more aggressive course, LR being highly predictable by PM and DM occurring in as many as 12.5% of pts. This should be used to inform treatment decision for the two DFSP variants. pts PM LR LR/PM DM C-DFSP 246 21 (8.5%) 2 (0.8%) 2/21 (9.5%) 0 (0%) FS-DFSP 24 2 (8.3%) 2 (8.3%) 2/2 (100%) 3 (12.5%) Total 270 23 (8.5%) 4 (1.5%) 4/23 (17.4%) 3 (1.1%)