tbuckley/cabot-search huggingface dataset:
Preliminary report of an open-label, multicenter, phase I/II study of AT-101 in combination with docetaxel (D) and prednisone (P) in men with docetaxel refractory prostate cancer
Authors: B. Poiesz, J. Reeves, W. McNulty, J. Maleski, J. Holmlund, L. Leopold
Journal: Journal of Clinical Oncology (2009)

5145 Background: Antiapoptotic Bcl-2 family proteins are overexpressed in castrate resistant prostate cancer (CRPC) and contribute to resistance to therapy. AT-101 is a pan-Bcl-2 inhibitor (Bcl-2, Bcl-X L, Bcl-W, and Mcl-1) and potent inducer of proapoptotic proteins. AT-101 is active as a single agent and in combinations with standard therapies in in vitro and in vivo tumor models, as a single agent in a phase II trial in CRPC, and in combination with D/P as first-line therapy in CRPC, as demonstrated by declines in PSA and RECIST responses. Methods: Men ≥18 years of age with docetaxel-refractory CRPC were eligible. Patients (pts) must have PSA progression per the Bubley criteria or documented disease progression while receiving prior D/P therapy. Pts (n = 40) were treated with D (75 mg/m 2 day 1), P (5mg b.i.d. on days 1–21) and AT-101 40mg b.i.d. on days 1–3 of each 21-day cycle. Safety (NCI CTCAE v3.0) and efficacy (Bubley Criteria for PSA) were assessed at 3-wk intervals. Radiological assessments were performed at 6-wk intervals for pts with soft tissue disease and bone scans were performed after cycle 6 and at the completion of therapy. Results: Efficacy data was available on 34 pts. Thirty-five percent (12/34) of pts treated had at least a 30% decrease in PSA level and 18% (6/34) of pts achieved a &gt;50% PSA decline. Twenty one of 34 pts included in this analysis had measurable disease. Five pts (24%) with measurable disease had a PR or CR by RECIST criteria and one additional patient had tumor shrinkage of 29%. Two (2) RECIST PRs are unconfirmed. Thus far, 3 pts have been on therapy for 6 months or more and 15 pts remain on study. Safety data was available on 22 pts. The most common (&gt;20%) adverse events (AEs) included fatigue (55%), anorexia, including weight decreased (45%), diarrhea and nausea (27%), vomiting and neutropenia (23%). The grade 3/4 AEs occurring in more than 1 pt were: neutropenia (5), anemia, anorexia, dyspnea and leukopenia (2 pts each). One partial small bowel obstruction was the only related, serious adverse event (SAE) reported to date. Conclusions: This data supports that AT-101 can be administered safely with D/P in pts with CRPC who are docetaxel-refractory. Durable PSA and RECIST responses were observed. [Table: see text]
Can't play, won't play: longitudinal changes in perceived barriers to participation in sports clubs across the child-adolescent transition
Authors: Laura Basterfield, Lauren Gardner, Jessica K Reilly, Mark S Pearce, Kathryn N Parkinson, Ashley J Adamson, John J Reilly, Stewart A Vella
Journal: BMJ (2016)

Background: Participation in sports is associated with numerous physical and psychosocial health benefits, however, participation declines with age, and knowledge of perceived barriers to participation in children is lacking. This longitudinal study of children and adolescents aimed to use the ecological model of physical activity to assess changes in barriers to participation in sports clubs to identify age-specific and weight-specific targets for intervention. Methods: Longitudinal study—Perceived barriers to sports participation were collected from a birth cohort, the Gateshead Millennium Study (n>500) at ages 9 and 12 years. The open-ended question ‘Do you find it hard to take part in sports clubs for any reason?’ was completed with free text and analysed using content analysis, and the social–ecological model of physical activity. Results: Barriers from across the social-ecological model were reported. Barriers at 9 years were predominantly of a physical environmental nature, and required high parental involvement (for transport, money, permission), or were associated with a lack of suitable clubs. At 12 years, perceived barriers were predominantly classed as intrapersonal (‘they’re boring’) or social environmental (‘my friends don’t go’). Perceived barriers were not associated with weight status. Conclusions: Perceived barriers to sports participation change rapidly in childhood and adolescence. Future interventions aiming to increase sports participation in children and adolescents should target specific age groups, should consider the rapid changes which occur in adolescence, and aim to address prominent barriers from across the socioecological model. Perceived barriers may be unrelated to current weight status, allowing for more inclusive solutions.
Phase I trial of NY-ESO-1/LAGE1 peptide vaccine for metastatic castration resistant prostate cancer (mCRPC).
Authors: Teresa Gray Hayes, Guru Sonpavde, Mingjun Wang, Yicheng Wang, Teresa Joe, Martha P. Mims, Michael M. Ittmann, Thomas M. Wheeler, Adrian P. Gee, Rongfu F Wang
Journal: Journal of Clinical Oncology (2012)

4643 Background: The NY-ESO-1 and LAGE-1 antigens are amplified in malignancies including prostate cancer. Preclinical induction of immune responses and anti-tumor activity has been demonstrated upon administration of these peptides. A phase I/II clinical trial evaluated the feasibility of a combined HLA class-I and class-II peptide vaccine in mCRPC. Methods: Men with progressive mCRPC, Performance Status ≤2, PSA ≥10 ng/ml and had appropriate HLA class I (A2) and class II haplotypes (DR4, DP4, DR13) were eligible. Three groups with 3 patients each received the vaccine subcutaneously every 2 weeks for 6 doses. Group 1 was treated with a peptide directed at a HLA class I haplotype (HLA A2), Group 2 was treated with a peptide reacting to a HLA class II haplotype (DR4, DP4, or DR13), and Group 3 received peptides directed at both Class I and II haplotypes. Group I and Group II received 1 dose of 1000 mcg and Group III received doses of 1000 mcg for each of 2 peptides. Androgen-deprivation was continued. Results: Of 14 patients enrolled, all were evaluable for toxicities and 9 patients completed all 6 treatments per amended protocol and were evaluable for efficacy. The median baseline PSA was 85.19 ng/ml. Four patients were chemo naive and 5 were post-docetaxel. One patient had a grade 5 event (myocardial infarction) unlikely therapy-related. Potential therapy related toxicities were local grade 1 injection site erythema (n=5), fatigue (n=2), flu-like symptoms (n=1), myalgias (n=1), anorexia (n=1), nausea (n=1) and leukocytosis (n=1). The median PSA doubling time pre-therapy and during therapy were 3.1 and 4.92 months, respectively. The PSA-DT was prolonged compared to baseline in 6 patients, including a negative PSA slope in 2 patients. Antigen-specific immune response determined by ELISPOT was observed, and its association with slowing of PSA-doubling time will be further examined. Conclusions: In men with mCRPC, HLA class-I and/or class-II restricted NY-ESO-1 and LAGE-1 peptides administered subcutaneously demonstrated excellent tolerability, slowing of PSA doubling time and antigen-specific immune responses. Further development of peptide vaccines alone or in combination with other regimens may be warranted.
Characteristics and outcome of patients with therapy-related acute promyelocytic leukemia front-line treated with or without arsenic trioxide
Authors: S Kayser, J Krzykalla, M A Elliott, K Norsworthy, P Gonzales, R K Hills, M R Baer, Z Ráčil, J Mayer, J Novak, P Žák, T Szotkowski, D Grimwade, N H Russell, R B Walter, E H Estey, J Westermann, M Görner, A Benner, A Krämer, B D Smith, A K Burnett, C Thiede, C Röllig, A D Ho, G Ehninger, R F Schlenk, M S Tallman, M J Levis, U Platzbecker
Journal: Leukemia (2017)
The effect of pretreatment psychosocial factors on immune function and quality of life after brief presurgical stress management.
Authors: Chelsea D. Gilts, Patricia A. Parker, Curtis A. Pettaway, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2012)

9031 Background: It is important to identify factors that predict who will benefit the most from psychosocial interventions in cancer populations. Methods: We examined the association between pretreatment psychosocial factors and subjective and objective outcomes from a brief cognitive-behavioral stress management program. This three-arm randomized clinical trial investigated the effects of a presurgical stress management (SM; n=53) compared to supportive attention (SA; n=54) and standard care (SC; n=52) on quality of life (QOL) and immune outcomes in men with prostate cancer scheduled for radical prostatectomy. We previously reported improved QOL 1 year after surgery in the SM and SA groups compared to the SC group and higher pro-inflammatory cytokines 48h after surgery in the SM group. We investigated the moderating effects of baseline psychosocial factors (social support (SS), dyadic adjustment (DA), distress (BSIGSI), and impact of event (IES)), on QOL (SF-36 physical (PCS) and mental (MCS) component scores) 1 year after surgery and immune response 48h after surgery. Results: Baseline SS and BSIGSI interacted with group in predicting PCS 1 year after surgery (p’s &lt;.05). Men who reported low baseline SS and were in SM had increased PCS 1 year after surgery compared to men with low SS in the SC group (b=.36, p&lt;.01). Conversely, men who reported high BSIGSI at baseline and were in SA had increased PCS 1 year after surgery compared to those in SM (b=11.14, p=.03), with SC having an intermediate nonsignificant effect. All four psychosocial factors (SS, DA, BSIGSI, IES) interacted with group in predicting changes in pro-inflammatory cytokines (interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor, and interferon) 48h post-surgery (all p’s &lt;.04). In all significant interactions, men who reported greater psychosocial vulnerability at baseline and were in SM had increased immune response 48h after surgery compared to psychosocially vulnerable men in either SC (all p’s &lt;.02) or SA (all p’s &lt;.02). Conclusions: These findings suggest that baseline psychosocial factors are important indicators of who may benefit most from a SM intervention on both subjective and objective outcomes.
Long-term results of the phase III GITMO/FIL trial of CHOP-R versus R-HDS plus autograft in high-risk follicular lymphoma (FL) at diagnosis.
Authors: Corrado Tarella, Fabio Benedetti, Carola Boccomini, Caterina Patti, Anna Maria Barbui, Alessandro Pulsoni, Maurizio Musso, Anna Marina Liberati, Guido Gini, Claudia Castellino, Fausto Rossini, Caterina Stelitano, Tommasina Perrone, Valerio Zoli, Paolo Corradini, Riccardo Bruna, Angela Gueli, Roberto Passera, Michele Magni, Marco Ladetto
Journal: Journal of Clinical Oncology (2014)

8531 Background: Early results of a randomized phase III GITMO/FIL study (www.clinicaltrials.gov NCT00435955) comparing CHOP-R vs. R-HDS + ASCT as primary treatment in134 FL pts, aged ≤60 yrs with aaIPI>1/IIL score>2, showed superior disease control with R-HDS but no OS advantage (Ladetto et al, Blood 2008). We here present an updated analysis from July 2013 at a median follow-up (MFU) of 9.5 yr including 125 pts of 134 originally randomized pts (61 CHOP-R/64 of R-HDS). Methods: Clinical features (CF) and treatment schedules have been already reported. Briefly, median age was 51 yrs. (22-60), M/F ratio 74/51, aaIPI 2-3 90%, retrospective FLIPI >2 60%, high LDH 49%, bulky disease 62%, B-symptoms 45%, BM+ 86%. CF were balanced among the two arms. Analysis was intention to treat and EFS the primary endpoint. Minimal residual disease was done by nested and RQ-PCR. Results: CR rate was 70.4% (57% with CHOP-R and 83% with R-HDS, p < .001); 64% patients achieved a Molecular Remission (MR). At MFU, 88 patients (70.4%) are alive. 19 pts died of lymphoma (CHOP-R:11; R-HDS: 8), 9 of second cancer (CHOP-R: 3; R-HDS: 6) and 9 for other causes, including 4 early toxic deaths. OS is 78% and 70% at 5 and 10 yrs, respectively. There was no difference in OS, with 5 and 10 yrs projections respectively of 75% and 70% for CHOP-R and 81% and 70% for R-HDS (p=0.96). Response to primary treatment had a major impact on OS, with 5 and 10 yr survival projections respectively of 90% and 80% for patients achieving CR, and of 49 and 43 for those with less than CR (p < .001). Similarly, MR achievement was associated with prolonged OS, with 5 and 10 yr survival projections respectively of 89% and 83% for patients achieving MR vs 76% and 57% for those remaining PCR-positive(p = .03). Conclusions: our results indicate that: i) 70% of high-risk FL now experiences a prolonged survival, being alive at 10 yrs; ii) the superior disease control of R-HDS does not translate in any OS advantage, iii) achieving CR and MR is crucial for long-term OS; iv) progression remains the major cause of death, though a major toll is paid to secondary neoplasms, particularly AML. Clinical trial information: NCT00435955.
Dual intervention with a lymph node (LN) specimen collection kit and enhanced specimen dissection to improve staging of resectable non-small cell lung cancer (NSCLC).
Authors: Srishti Sareen, Robert A. Ramirez, Ahmed Yasir Javed, Laura Elizabeth Miller, Christopher Wang, Matthew Smeltzer, Alim Khandekar, Glenn P Schoettle, Samuel G Robbins, Jeffrey B Gibson, Bradley Aaron Wolf, Edward T Robbins, Raymond U Osarogiagbon
Journal: Journal of Clinical Oncology (2013)

7569 Background: LN metastasis impairs survival of resectable NSCLC, but routine pathologic nodal staging is suboptimal. We tested the impact of a dual intervention (a surgical specimen collection kit with specific, pre-labeled LN collection cups, to improve intraoperative hilar/mediastinal LN dissection; and a fastidious gross dissection of the resected lung specimen for perihilar/intrapulmonary LNs) on the rate of detection of LN metastasis. Methods: We matched dual intervention cases with controls performed with standard surgical specimen collection and pathology examination protocols. Controls were hierarchically matched for extent of resection, laterality, surgeon, pathologist and T-stage. All statistical comparisons were made with Exact Conditional Logistic Regression, to account for the matched case-control design. Results: Patient demographic, tumor histology, and size characteristics were similar between the groups. The impact of the dual interventions is shown in the Table. Conclusions: The dual interventions significantly increased retrieval of N1 and N2 LNs, the rate of detection of LN metastasis, and nodal up-staging. There were strong trends towards higher aggregate stage and increased adjuvant therapy eligibility. The interventions may improve stage-adjusted survival by improving stage accuracy, and improve aggregate survival by increasing the appropriate use of post-operative adjuvant therapy. A prospective randomized trial to test survival impact of the dual interventions is at an advanced planning phase. [Table: see text]
Levosimendan for Hemodynamic Support after Cardiac Surgery
Authors: Giovanni Landoni, Vladimir V. Lomivorotov, Gabriele Alvaro, Rosetta Lobreglio, Antonio Pisano, Fabio Guarracino, Maria G. Calabrò, Evgeny V. Grigoryev, Valery V. Likhvantsev, Marcello F. Salgado-Filho, Alessandro Bianchi, Vadim V. Pasyuga, Massimo Baiocchi, Federico Pappalardo, Fabrizio Monaco, Vladimir A. Boboshko, Marat N. Abubakirov, Bruno Amantea, Rosalba Lembo, Luca Brazzi, Luigi Verniero, Pietro Bertini, Anna M. Scandroglio, Tiziana Bove, Alessandro Belletti, Maria G. Michienzi, Dmitriy L. Shukevich, Tatiana S. Zabelina, Rinaldo Bellomo, Alberto Zangrillo
Journal: New England Journal of Medicine (2017)

Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery.
The effects of oncologists’ physical activity recommendations and information packages on level of physical activity and the quality of life in cancer survivors.
Authors: Ji-Hye Park, Yong Jin Yoon, Chul Won Lee, Junga Lee, Minsuk Oh, Jisuk Chae, Hyuna Park, Sanghui Chu, Seung Il Kim, Nam Kyu Kim, Lee Jones, Justin Y Jeon
Journal: Journal of Clinical Oncology (2014)

9629 Background: Physical activity participation has been associated with reduced cancer-specific and all-cause mortality in breast and colorectal cancer survivors. The purpose of this study was to examine the effects of oncologists’ recommendations of physical activity with and without information packages on physical activity on the amount of physical activity and quality of life in cancer survivors. Methods: A total of 161 stage I~III breast and colorectal cancer survivors, who were 52.08±8.21 years old were recruited for this study. They were assigned to one of three groups: 1) control group, 2) oncologists’ recommendations for physical activity group, and 3) oncologists’ recommendations for physical activity combined with information packages group. At baseline and after 4 weeks, the level of physical activity was measured using the Godin Leisure-Time Exercise Questionnaire. Quality of life, including self-reported physical function, was measured with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. Results: Out of 161 participants, 130 participants completed the trial (78.8%). Our study found that participants who received oncologists’ physical activity recommendations with information packages significantly increased their levels of physical activity compared with the control group (pre: 9.91±7.75 vs. post: 14.21±11.89 Metabolic Equivalent of Task (MET) hours per week, p<0.01).Participants who only received oncologists’ physical activity recommendations did not increase their physical activity levels. Furthermore, the pain levels of participants who received physical activity recommendations with information packages were significantly reduced after 4 weeks compared with those of the control group. Conclusions: It is important to provide physical activity information packages in addition to oncologists’ recommendations in order to increase levels of physical activity among breast and colorectal cancer survivors. This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(2013R1A1A2005986).
Quality of life in intermediate or high risk prostate cancer patients treated by 3-D external beam radiotherapy and brachytherapy with or without androgen deprivation
Authors: B. Guix, T. M. Lacorte, F. Guedea
Journal: Journal of Clinical Oncology (2006)

14587 Background: To elucidate long-term changes in health-related quality-of-life (HRQOL) outcomes by prospectively re-evaluating a cohort of intermediate- or high-risk prostate cancer patients treated by a combination of 3-D External Beam Radiotherapy (EBRT) and Brachytherapy (BT) with or without androgen deprivation (AD). Methods: A cross-sectional survey was administered to 200 consecutive patients with intermediate (Gleason 7 or PSA 10–20 or T2A-B) or high (Gleason &gt;7 and/or PSA &gt;20 and/or &gt;T2B) - Risk Prostate cancer who were treated by EBRT to the prostate followed by BT to the prostate given either by permanent 125-I seeds (LDR) or high dose rate (HDR) implants before treatment and at 6 months interval during 4 years follow-up. The EORTC CLQ-C30 with the PR-25 module was employed. HRQOL was compared among therapy groups. Comparisons between therapy groups was performed using regression models to control covariates. HRQOL of treatment parameters were evaluated. Distribution of responses for bowel-, urinary- and sexual-related functions were analyzed. Results: 200 patients completed the questionnaires. Significant changes in HRQOL were found depending of the time after treatment. After a temporal decline in HRQOL, an improvement owas found during the first 18 months after end of treatment. Significant improvement in the urinary irritative-obstructive performance (p &lt; 0.006) was found after 6 months post-treatment. Bowel domains worsened after therapies (p &lt; 0,05) but improved after 18 months follow-up (p &lt; 0.02). Overall sexual HRQOL deteriorated depending greatly on treatment (p &lt; 0.008). Patients who were given AD presented a significant lower Sexual Function values, that were difficult to recover after AD cessation (p &lt; 0.007). No differences in HRQOL were found between LDR or HDR BT implants. Satisfaction with either treatment was high. Conclusions: After a decline in HRQOL after treatment, it recovered fully during follow-up. In patients treated by AD, sexual function was the most adversely affected quality-of-life domain. Sexual impairment induced by AD was difficult to recover. These results may be of assistance to men and to clinicians when making treatment decisions, mainly relating AD. No significant financial relationships to disclose.
Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages
Authors: Catherine Sabatel, Coraline Radermecker, Laurence Fievez, Genevieve Paulissen, Svetoslav Chakarov, Claudia Fernandes, Sabine Olivier, Marie Toussaint, Dimitri Pirottin, Xue Xiao, Pascale Quatresooz, Jean-Claude Sirard, Didier Cataldo, Laurent Gillet, Hicham Bouabe, Christophe J. Desmet, Florent Ginhoux, Thomas Marichal, Fabrice Bureau
Journal: Immunity (2017)
Prognostic factors for the efficacy of catumaxomab in patients (pts) with malignant ascites (MA): Meta-analysis from two phase III studies.
Authors: Hilke Friccius-Quecke, Markus M. Heiss, Florian Lordick, Simon L. Parsons, Pauline Wimberger, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2013)

3078 Background: Data from two phase III studies (IP-REM-AC-01 and CASIMAS) were used for a meta-analysis to identify factors with a potential impact on the efficacy of catumaxomab (CATU) in pts with MA. Methods: 389 pts treated with CATU plus paracentesis and 88 control pts (paracentesis only) were included. Efficacy parameters were overall survival (OS), puncture-free survival (PuFS) and time to first puncture (TTPu). The impact of the prognostic factors Karnofsky Index (KI), total serum protein (protein) and presence/absence of distant metastases (metastases) at inclusion was analysed for these parameters. Results: Pts treated with CATU showed a significant prolongation of PuFS (44 vs 11 d, HR 0.34, p&lt;0.0001), TTPu (88 vs 13 d, HR 0.26, p&lt;0.0001) and OS (88 vs 68 d, HR 0.62, p=0.007) compared to control pts. Pts treated with CATU and a KI of 80–100 at inclusion had significantly better OS compared to those with a KI of 60–79 (120 vs 57 d, HR 0.55, p&lt;0.001) and improved PuFS (55 vs 27 d, HR 0.61, p&lt;0.001) but not improved TTPu (88 vs 96 d, HR 0.80, p=0.186). Linear Cox regression of KI as a co-variable showed a significantly positive impact of high KI on catumaxomab efficacy for OS (HR 0.97, p&lt;0.001) and PuFS (HR 0.98, p&lt;0.001) but not TTPu (HR 0.99, p=0.054). Cox regression analysis of the presence of distant metastases and low (&lt; normal) total serum protein on CATU efficacy showed a negative impact on OS (metastases: HR 1.43; p&lt;0.001; protein: HR 1.39, p=0.002), PuFS (metastases: HR 1.37, p=0.003; protein: HR 1.45, p&lt;0.001) and TTPu (metastases: HR 1.28, p=0.069; protein: HR 1.41, p= 0.011). Treatment effects on PuFS and TTPu were observed in all subgroups for all factors but the effect on OS compared to controls was only found in pts with KI 80–100 and in those with no distant metastases and with normal/high total serum protein. Conclusions: Karnofsky Index, distant metastases and total serum protein at screening were identified as factors having a significant impact on OS in CATU-treated pts and better prognostic pts compared to controls. In contrast, the effect of CATU on ascites control (PuFS, TTPu) was observed in all subgroups irrespective of whether the pts were in the good or poor prognostic group.