tbuckley/cabot-search huggingface dataset:
Age-related changes in plasma levels of inflamatory and angiogenic cytokins in patients with cancer.
Authors: J. Spano, P. Chaïbi, S. Vignot, J. C. Thery, T. de La Motte Rouge, M. Gil-Delgado, D. Khayat, R. Mouawad
Journal: Journal of Clinical Oncology (2011)

e19699 Background: The majority of cancer incidence and mortality occurs in individuals aged older than 65 years, and the number of older adults with cancer is projected to significantly increase. As such, understanding the changes accompanying age in the context of the cancer patient is of critical importance. Age-related changes can impact tolerance of anticancer therapy and can shift the overall risk-benefit ratio of such treatment. It is increasingly recognized that several laboratory markers may predict morbidity and mortality in older adults; these biologic variables may further aid in stratifying this group of patients based on risk. In this study we evaluated. In this study we examine inflammatory and angiogenic markers in cancer patients classified according to there age in older adults. Methods: Using ELISA test circulating Il-6, TNF alpha and vegf were measured in the sera of 80 patients with different cancer of whom 38 (48%) were female in comparison to 40 healthy controls.Three groups of patients were studied, the first consisted of 25 patients (age 30-40 years); the second of 25 (age 40-70 years), the third group of 30 elderly persons (>70 years). Results: Serum IL-6 and VEGF levels were higher in cancer patients as compared to control group.serum IL-6, TNF alpha and VEGF levels were higher in cancer patients as compared to control group. When patients were classified according to their age, a significant age-related increase of IL-6 and VEGF were observed (p=0.009 and 0.034 respectively) but not with TNF alpha. Furthermore, high IL-6 and VEGF level were associated with further functional adverse outcomes. Conclusions: A specific inflamatory and angiogenic status exist for elderly patients. the increased level of these markers might predispose these patients to clinical manifestations and non tolerence of the treatment. However, a study comparing these parameters only in elderly patients (> 70 years) and relation to there clinical status are necesseary to confirme these results.
Exploratory analysis of the effect of ruxolitinib on bone marrow morphology in patients with myelofibrosis.
Authors: Hans-Michael Kvasnicka, Juergen Thiele, Carlos E. Bueso-Ramos, Kevin Hou, Jorge E. Cortes, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2013)

7030 Background: Myelofibrosis(MF) is characterized by splenomegaly, burdensome symptoms, progressive bone marrow (BM) fibrosis, and shortened survival. Ruxolitinib (Rux), an oral, FDA-approved JAK1/JAK2 inhibitor, has demonstrated improvements in spleen volume, symptoms, and survival in patients (pts) with MF. This study was conducted to explore possible effects of long-term Rux treatment on BM morphology in MF. Methods: Trephine biopsies were obtained at baseline, 24 (67 pts), and 48 (17 pts) months (mo) from the cohort of MF patients treated at MD Anderson Cancer Center who participated in a phase I/II trial of Rux (NCT00509899). The clinical outcomes from this trial have been published previously [Verstovsek, NEJM 2010]. Two of the authors (JT and HMK) independently evaluated the World Health Organization (WHO)-defined BM fibrosis grade (0-3). Reviewers were blinded to pts characteristics and outcomes and consensus decided discordant scores. For demonstrative purposes, WHO BM fibrosis grading was also determined for a control cohort of pts treated with hydroxyurea (HU) for 24 (31 pts) and 48 (20 pts) mo. Changes in BM fibrosis grade vs. baseline were calculated for 24 and 48 mo, and categorized as improvement, stabilization, and worsening for each patient. Results: A higher percentage of Rux-treated pts showed stabilization or improvement of BM fibrosis at both 24 and 48 mo than the HU-treated pts. Worsening was greater in the HU-treated cohort at both time points. Conclusions: This exploratory analysis of long-term exposure to Rux in MF provides the first indication that JAK inhibitor therapy may be able to meaningfully retard advancement of BM fibrosis. A comparable effect was not seen with long-term HU therapy. Additional research is needed to further elucidate these findings. Clinical trial information: NCT00509899. [Table: see text]
Association of PIK3CA kinase domain mutations with poor prognosis in operable breast cancer.
Authors: A. Voutsina, A. Kalikaki, V. Mitsi, E. Stathopoulos, V. Georgoulias, D. Mavroudis
Journal: Journal of Clinical Oncology (2011)

e21060 Background: The PI3K pathway is frequently altered in breast cancer (BC) and may contribute to therapeutic resistance and clinical outcome. However, the findings concerning the impact of PIK3CA mutations on BC are controversial. The aim of this study was to characterize the PIK3CA mutations in a cohort of 101 operable BC patients receiving systemic adjuvant therapy and to determine associations with pathological features and patient outcome. Methods: Mutations in the helical (E542K, E545K) and the kinase (H1047R, H1047L) domains of the PIK3CA gene were investigated by direct sequencing and Amplification Refractory Mutation System (ARMS) allele-specific PCR and Scorpion probes in FFPE tumor samples. The prognostic significance of PIK3CA mutations for disease-free survival (DFS), and overall survival (OS) was evaluated in univariate and multivariate analysis adjusted for the type of surgery (breast-conserving vs mastectomy), adjuvant treatment administered, histological grading, tumor size, axillary node infiltration, menopausal status, estrogen (ER) as well as progesterone (PR) receptor and HER-2 status. Results: PIK3CA mutations were detected in 21(21%) of the primary tumors (E542K in one, E545K in 4, E545D in one, H1047R in 11 and H1047L in 4) and were significantly associated with PR+ BC (p=0.036). After a median follow-up of 60.5 (range 4.6-199) months 27 (27%) patients had relapsed and 18 (18%) had died. PIK3CA kinase domain mutations were associated with significantly shorter DFS (p=0.001) and OS (p=0.012). Multivariate analysis showed that PIK3CA kinase domain mutations, nodal involvement and tumor size were independent prognostic factors for OS. The relative risk of death in patients with PIK3CA kinase domain mutations was 7.68 (95% CI = 2.22-26.57, p=0.001). Conclusions: Our results suggest that PIK3CA kinase domain mutations are an independent risk factor for poor prognosis in operable breast cancer patients.
Antigen-specific immune responses through 24 months in the STAND trial: A randomized phase 2 study evaluating optimal sequencing of sipuleucel-T (sip-T) and androgen deprivation therapy (ADT) in biochemically-recurrent prostate cancer (BRPC).
Authors: Emmanuel S. Antonarakis, Adam S. Kibel, George W. Adams, Lawrence Ivan Karsh, Aymen Elfiky, Neal D. Shore, Nicholas J. Vogelzang, John M. Corman, Robert Claude Tyler, Candice McCoy, Todd DeVries, Nadeem A. Sheikh, Charles G. Drake
Journal: Journal of Clinical Oncology (2015)

171 Background: Sip-T is an autologous cellular immunotherapy targeting prostatic acid phosphatase (PAP), approved for treatment of asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer. STAND evaluates sequencing of sip-T and ADT in men with BRPC at high risk of metastases. Here we report interim assessments of cellular and humoral responses through 24 mos. Methods: Men (n=68)were randomized 1:1 to sip-T followed by ADT (2 wks after 3rd infusion; Arm 1) or ADT (3-mo lead-in) followed by sip-T (Arm 2). Product parameters (total nucleated cell [TNC] count, antigen presenting cell [APC] count, APC activation) were determined with each product manufacture. Cellular and humoral immune responses were analyzed through 24 mos with a repeated measures statistical model. Results: Sample size ranged 8–28 for cellular responses and 34–64 for humoral responses. PA2024 ELISPOT count increased vs baseline at most timepoints (p&lt;0.05) and was lower in Arm 2 vs Arm 1 (p=0.015). PA2024 antigen-specific T-cell proliferation increased from baseline at all timepoints (p≤0.001) and was lower in Arm 2 vs Arm 1 (p&lt;0.001). PA2024 antibody titers were similar between treatment arms (p=0.976). PA2024 antibody titer was significantly higher at the 3rd sip-T infusion visit and remained elevated at 24 mos (23 times higher on average vs baseline; p&lt;0.001). A similar antibody titer profile was reported for PAP but of lesser magnitude. The number of immune responders (post-baseline antibody titer ≥25,600) was similar at any timepoint between arms (Arm 1: 30/34, 88.1%; Arm 2: 32/34, 94.1%; p=0.673). Higher cumulative TNC and baseline hemoglobin positively correlated with maximum PA2024 antibody titer response (p&lt;0.05). Conclusions: Sip-T induced a robust immune response sustained to 24 mos in men with BRPC. Cellular response appeared to differ according to treatment sequence; humoral response was similar between treatment arms. Given its consistent association with the humoral response, cumulative TNC count may be a potential biomarker of response to sip-T. Clinical trial information: NCT01431391.
Safe negative-margin width in breast-conservative therapy: Results from a population with a high percentage of negative prognostic factors.
Authors: Abu Bakar Hafeez Bhatti, Amina Iqbal Khan, Muhammad Awais Aamir, Mazhar Ali Shah, Neelam Siddiqui, Narjis Muzaffar
Journal: Journal of Clinical Oncology (2013)

75 Background: There remains a controversy in literature regarding adequate width of negative surgical margins in breast conservative therapy (BCT). Majority of patients included in studies on outcomes of BCT had favorable prognostic factors. Pakistani population is known to have an elevated expression of unfavorable prognostic factors. This study was done to determine safe negative margin width in a patient population with significantly higher percentage of unfavorable prognostic factors undergoing BCT. Methods: A review of patients who received BCT from 1997-2009 at Shukat Khanum Cancer Hospital was performed. A total of 603 patients whose margin status could be assessed were included. Patients were divided into close ( ≤ 2mm), free (&gt; 2-10mm), and wide (&gt; 10mm) margin groups. Patient characteristics, medical treatment modalities, and number of locoregional recurrences were observed for each margin group. Chi square and Fisher’s exact test were used for categorical variables. Five year locoregional control was determined for margin groups. Univariate and multivariate Cox regression analysis was performed to determine independent predictors of locoregional recurrence. Results: Out of total, 415 (69%) patients were &lt;50 years of age. There were 82 (15%) T3/T4, 337 (56%) poorly differentiated and 238 (39%) ER/PR–ve tumors. Nodal positivity was present in 314 (52%) patients. A higher percentage of T3/T4 tumors in close margin group (25% versus 13% and 7%) (p &lt; 0.0001) was observed. Use of neoadjuvant chemotherapy was significantly higher in close margin group (33% versus 29% and 16%) (p &lt; 0.0001). The actual number of observed locoregional recurrences was 16 (12%), 8 (3%), and 10 (4.6%) in close, free, and wide margin groups (p = 0.002) while the expected 5 year locoregional control was 90%, 97%, and 96% (p = 0.002) respectively. On multivariate analysis tumor size stage, nodal involvement and negative margin width were independent predictors of locoregional failure. Conclusions: A negative margin width of 2mm might represent an adequate negative margin width in populations with a higher percentage of unfavorable prognostic factors.
Overview Of The Genomic Landscape Of High Risk Diffuse Large B-Cell Lymphoma Using Targeted DNA and RNA Sequencing
Authors: Kai Wang, Michelle Nahas, Anthony R Mato, Amy L Donahue, Jie He, Geoff A Otto, Doron Lipson, Roman Yelensky, Jeff Ross, Phil Stephens, Kar Fai Chow, Tania Zielonka, Pritish K. Bhattacharyya, Ewelina Protomastro, Tatyana Feldman, Andrew L. Pecora, Vincent Miller, Andre Goy
Journal: Blood (2013)
Using information technology (IT) to improve communication between the emergency room and cancer clinic.
Authors: Katelyn Sarah Balchin, Conrad B Falkson, Tara D. Baetz
Journal: Journal of Clinical Oncology (2016)

158 Background: A communication gap was identified at the Cancer Centre of Southeastern Ontario which resulted in oncologists at the cancer centre (CC) not consistently being informed when oncology patients (pt) were seen in the emergency room (ER). An automated IT notification system was developed to inform oncologists when their pt were seen in the ER. Methods: Pt who had been seen within 60 days in the CC were considered active. An IT notification system linked active CC visits and ER visits. A list was generated daily of pt that were both CC and in the ER and this was emailed through a secure system to treating oncologists. Following six months of usage an evaluation was performed which identified which pt were being seen in ER (by disease site, treatment regimen and other factors). A survey evaluated oncologist feedback regarding usefulness of this system. Results: From December 2014 to May 2015 notifications were analyzed. A total of 773 pt (12% of total active cancer patients) had an ER visit resulting in 1267 visits; 56% of pt had more than one visit. Thirty-three percent of visits result in admission to the hospital. The highest usage of the ER was palliative care (26% of pt) and hematology (29% of visits). The risk of dying in the three months following an ER visit was 20% as compared to &lt; 2% for all pt seen in the ER during that time period. Sixty-three percent of the 41 oncologists responded to a survey. The majority used this notification system (85%) and found that the report improved patient care (87%). Oncologists typically used this information to check up on pt information on the electronic medical record and if appropriate visited pt that had been admitted to hospital. Conclusions: Cancer pt who have an ER visit are now automatically being reported to the treating oncologists. This process has been able to identify at risk pt for ER visits and this information will be used to develop targeted measures for these high risk populations. The report is very popular with oncologists and is now considered standard practice at our CC.
SCIO-469, a Potent and Selective Inhibitor of p38a MAPK, Normalizes the Bone Marrow Microenvironment and Inhibits Multiple Myeloma Cell Proliferation in In Vitro and In Vivo Models.
Authors: Aaron N. Nguyen, Mamatha Reddy, Margaret Henson, Elizabeth G. Stebbins, Gilbert O’Young, Jing Y. Ma, Edwin Haghnazari, Ann M. Kapoun, Satya Medicherla, Andy Protter, Tony A. Navas, Linda S. Higgins
Journal: Blood (2004)
Low preoperative platelets to predict postoperative liver dysfunction in patients with metastatic colorectal cancer undergoing liver resection.
Authors: Patrick Starlinger, Beata Herberger, Dietmar Tamandl, Stefan Stremitzer, Christine Brostjan, Birgit Gruenberger, Thomas Gruenberger
Journal: Journal of Clinical Oncology (2012)

634 Background: Despite improving median survival of metastatic colorectal cancer (mCRC) patients, chemotherapy (CTx) compromises liver function. Therefore, selection of patients who are of high risk to develop liver dysfunction (LD) after surgery is important. As platelets are of major importance in liver regeneration, we investigated the impact of preoperative platelet counts on the incidence of postoperative LD and its correlation to postoperative morbidity and mortality. Methods: Patients treated with liver resection for mCRC between January 2000 and December 2010 were eligible. LD was defined as bilirubin &gt; 5 mg/dL or prothrombin time &lt;50% within the first postoperative week. The association of preoperative platelets &lt; 150 x 10 3 /ml with LD, 90 days mortality and surgical complications was analyzed. Results: 518 patients with metastatic CRC cancer underwent liver resection, of whom 68% had received neoadjuvant CTx. 21% of all patients developed LD. Postoperative complications occurred in 13.5%. 10 patients died within 90 days after liver resection (1.9%). The incidence of LD and complications was significantly higher in patients with preoperative platelets &lt; 150 x 10 3 /ml (P=0.010, P=0.047). 90 days mortality was nearly 3 times higher in patients with reduced preoperative platelets (9.8% vs. 3.7%). Neoadjuvant CTx was associated with an increased rate of platelets &lt; 150 x 10 3 /ml (with CTx 25%, without CTx 17%; P=0.051), LD (with CTx 23%, without CTx 15%; P=0.029) and postoperative mortality (with CTx 5.3%, without CTx 2.5%). Conclusions: Patients with platelets &lt; 150 x 10 3 /ml have an increased incidence of postoperative LD, major complications and 90 days mortality. Using this simple routine parameter, it might be possible to select patients that could be better served with alternative treatments such as radiofrequency ablation. Furthermore, reduced platelet counts and the incidence of LD were more frequent in patients after neoadjuvant CTx resulting in an increased 90 days mortality. This suggests that patients after extensive CTx accompanied by low platelets are of high risk to suffer from postoperative complications and surgical treatment should be reconsidered.
Phase II Study of Lenalidomide in Combination with Rituximab for Patients with CD5+/CD20+ Hematologic Malignancies Who Relapse or Progress After Rituximab. Interim Analysis.
Authors: Marays Veliz, Ricardo Santana, Jeffrey E Lancet, Rami S. Komrokji, Mohamed A Kharfan-Dabaja, John J. Powers, Jason A Dubovsky, Sara Tinsley, Darcie Deaver, Eduardo M. Sotomayor, Javier Pinilla-Ibarz
Journal: Blood (2009)
A pilot study of high-dose exisulind in men with biochemical relapse (BCR) of prostate cancer after definitive local therapy treated with intermittent androgen deprivation (IAD).
Authors: Evan Y. Yu, Kevin F Kuo, Rachel Hunter-Merrill, Roman Gulati, Heather H. Cheng, Jason Frederick Flamiatos, Teresa E Gambol, Suzanne P Hall, Celestia S. Higano
Journal: Journal of Clinical Oncology (2013)

209 Background: Exisulind is an apoptotic drug shown in vitro to inhibit expression and function of the androgen receptor. At lower doses as a single agent and in combination with chemotherapy it has demonstrated limited efficacy. In this pilot study, the potential for high dose exisulind to prolong the duration of the off treatment interval of IAD was studied. Methods: Eligible patients (pts) underwent prior definitive local therapy, had BCR, and received at least one full prior cycle of IAD, defined as a 9-month on- and variable off-treatment period (terminated by reaching PSA threshold 1 ng/mL for radical prostatectomy and 4 ng/mL for radiation). Exisulind (250 mg po bid) was started 3 months before completing the 2nd on-treatment period and continued through the 2nd off treatment interval and other IAD cycles until castration resistance (CRPC). We used a Cox proportional hazards model to estimate the association between receiving exisulind and time to resuming AD for pts who initiated exisulind during their 2nd on-treatment period. The model controlled for 1st off-treatment duration. Results: Nineteen pts were enrolled and treated with exisulind. Median age was 62 (range 50-75) years. Median PSA at diagnosis was 11 (3.9-99) ng/mL and 5 (1-19.2) ng/mL at initiation of IAD. Median Gleason score was 8 (6-9). Median duration of exisulind treatment was 1.5 (0.5-7.7) yrs and median follow-up was 9.3 (1.1-10.1) yrs. In 9 evaluable pts, taking exisulind was associated with a non-significant prolongation of the off treatment interval (15% decreased risk of progressing to PSA threshold and the next AD cycle, HR 0.85, 95% CI 0.41, 1.75, p=0.654). Six pts (32%) required at least one dose hold, 9 (47%) underwent a dose reduction for toxicity, and 7 (37%) came off trial for drug toxicity. Most common adverse events were elevated liver function tests (53%) and fatigue (42%). Median time to CRPC was 5.5 (0.3-not reached) yrs. Conclusions: High-dose exisulind was poorly tolerated and did not clearly extend the duration of 2 nd off-treatment intervals compared to the 1st. More potent contemporary agents may be more beneficial in this setting. Clinical trial information: NCT00283803.
Use of immunohistochemical evaluation of DNA repair proteins to demonstrate cisplatin response prediction in resected NSCLC squamous cell carcinoma.
Authors: W. E. Pierceall, K. M. Sprott, E. Brambilla, R. Pirker, H. H. Popper, X. Wang, Y. Chen, S. Quan, M. Filipits, L. Alaparthi, J. Kutok, D. T. Weaver, M. Al-Adhami, F. Andre, T. Le Chevalier, B. E. Ward, J. Soria
Journal: Journal of Clinical Oncology (2011)

10579 Background: Platinum-based chemotherapy remains the standard of care for many solid tumor malignancies including non-small cell lung cancer (NSCLC). The mechanism of action is related to the accumulation of DNA adducts that in turn activate pro-apoptotic pathways. An intense area of focus is the identification of molecular biomarkers of DNA adduct repair that may be predictive/prognostic for treatment of NSCLC patients. A complex network of compensating DNA repair pathways exists so interrogation of multiple DNA repair markers may be more informative in predicting cisplatin efficacy than individual markers. Additionally, biomarker expression may be utilized to define treatment of histological subclasses of NSCLC. Methods: International Adjuvant Lung Cancer Trial (IALT) NSCLC FFPE patient specimens constructed on TMAs were stained by IHC for DNA repair biomarkers: ATM, MSH2, ERCC1, p53, pMK2, PARP1, BRCA1, XPF. An average of 603 patients were analyzed for each. Tumor biomarker nuclear or cytoplasmic levels were determined using digital image user defined macros. Scores were generated based on weighted intensity and quantity of stained cells. Cox PH models adjusted for relevant clinical and stratification variables were used in the univariate analyses of DFS. Results: The univariate biomarker analyses yielded significant prognostic and predictive values using disease-free survival (DFS) as the primary endpoint. This exploratory data support predictive modeling of DNA repair enzyme expression levels that cosegregate with SCC but not adenocarcinoma, and include MSH2 (predictive p = 0.012, HR=1.218, 95%CI=[1.044-1.42]), p53 (p=0.005, HR=1.120, 95%CI=[1.035-1.212],) and ATM (p=0.010, HR=1.212, 95%CI=[1.046-1.405]). Partition models for pMK2, p53, ERCC1, ATM, and PARP1 were statistically significant for prediction in SCC but not adenocarcinoma. Conclusions: These data suggest that expression of DNA repair enzymes represent a distinct molecular difference between SCC and adenocarcinoma and that application of biomarker modeling may be predictive for specific tumor histological subclasses.