tbuckley/cabot-search huggingface dataset:
Genomic predictors of biochemical failure following radical prostatectomy.
Authors: Sanjay Aneja, James B. Yu, Peter Glazer
Journal: Journal of Clinical Oncology (2016)

114 Background: Although clinical correlates can help predict biochemical failure (BF), genomic correlates have yet to be identified. We hypothesized there would exist genomic profiles in patients who experience BF after radical prostatectomy (RP), for whom aggressive regional therapy may be more appropriate. Methods: Genes of interest were identified using the 25 most commonly mutated genes from the COSMIC dataset. The Cancer Genome Atlas (TCGA) was used to study normalized microarray gene expression data for patients who underwent RP for treatment of Gleason 7-10, T1/T2 N0 prostate adenocarcinoma. BF was considered PSA &gt; 0.1 following prostatectomy. Clinical data of interest included age, pre-treatment PSA, Gleason score, pathologic T stage, and country of origin. A multi-level hierarchical logistic regression model clustered with random effects by pathologic T stage and country of origin was built to identify predictors of BF. Variances were used to estimate how genomic differences explained differences in BF. Results: We identified 296 patients with T1/T2 N0 prostate adenocarcinoma who underwent RP. Median age was 60 with a median follow up of 2.3 years. 59% (n = 177) had Gleason 7 disease and 54% (n = 154) had T1 disease. 40.8% (n = 121) of patients had BF following RP. After adjusting for clinical covariates, 4 genes were associated with differences in BF. Specifically, increased RNA expression of E2F3 (OR 1.11 p &lt; .001), CTNNB1 (OR 1.49, p = .002), and AR (OR 1.21, p &lt; .001) were seen in patients who experienced BF. Expression of TP53 (OR 0.75, p &lt; .001) and Gleason 7 disease (OR 0.62 vs. Gleason 8-10, p &lt; .001) were associated with decreased likelihood of BF. Clustering by pathologic T stage accounted for 10% of variance in BF indicating that the 4 genes augment clinical patient characteristics. Conclusions: Genomic data augments pre-treatment clinical data in the stratification of patients undergoing RP. RNA expression of E2F3, CTNNB1, AR and TP53 is associated with differences in BF following RP. Clinically, these genes could aid in identifying patients who may benefit from more aggressive therapy. Further studies of the relationship between these genes and the development of prostate cancer could aid in future targeted therapies.
Factors associated with increased incidence of toxicities following administration of yttrium-90 resin microspheres.
Authors: John Roberson, Andrew M. McDonald, Craig Joseph Baden, Rojymon Jacob, Omer L. Burnett
Journal: Journal of Clinical Oncology (2015)

409 Background: To further define factors associated with increased incidences of hepatic, constitutional, and gastrointestinal toxicities following administration of yttrium-90 ( 90 Y) microspheres in a sequential cohort of heterogeneous patients. Methods: Fifty-seven patients who underwent 76 treatments were assessed for toxicity incidence following 90 Y administration. Post-treatment clinical and liver function test (LFT) toxicities were assessed using Common Terminology Criteria for Adverse Events version 4.03. Binary logistic regression was used to evaluate the univariate effect of factors on toxicity incidences. A multivariate binary logistic regression model was performed for each toxicity using all factors with a p &lt; 0.10 on univariate analysis. Results: Hepatic toxicities, including LFT toxicities, were present following 46.1% of treatments, while gastrointestinal and constitutional toxicities were present following 57.3% and 55.3%, respectively. Multivariate analyses revealed that colorectal adenocarcinoma, age at time of treatment, intraprocedural stasis, decreased Karnofsky Performance Status, increased body mass index (BMI), and decreased lung shunt were statistically significant (p &lt; 0.05) predictors for increased incidence of toxicities most prevalent among our cohort. Increased pre-treatment laboratory values including albumin, alkaline phosphatase, total bilirubin, and white blood cells were also statistically significant predictors. Conclusions: Colorectal adenocarcinoma, declining functional status, decreased lung shunt, and increased pre-treatment laboratory values should be given more clinical attention when attempting to limit toxicities and improve the quality of life in patients following 90 Y treatment. Specific constitutional, gastrointestinal, and hepatic toxicities including weakness, loss of appetite, and laboratory abnormalities are also associated with patients’ age, increased BMI, and intraprocedural stasis.
Breast cancer: Role of tumor associated antigens and regulatory cells [CD4+CD25+] as targets of the Immune response elicited by an anti-progressive autologous hemoderivative vaccine
Authors: E. Garcia-Giralt, E. Lasalvia-Prisco, S. Cucchi, J. Vázquez, E. Lasalvia-Galante, W. Golomar
Journal: Journal of Clinical Oncology (2005)

2589 Background: In advanced cancer from different primary tumors, our team (E. Lasalvia-Prisco et al, Cancer Biology & Therapy, 2003*; ASCO 2003, ASCO 2004) has reported anti-tumoral effect of an immunotherapy procedure using as immunogen an autologous hemoderivative (AHD). We explored in a breast cancer population the immunological mechanisms involved. Methods: Patients.- Metastatic breast cancer patients (n= 121), hormone/chemotherapy resistant, high CEA/CA 15–3 plasma levels, PS<3 and documented progressive disease were 2-group randomized: AHD-vaccinated as reported* and controls. Assessment.- Clinical response: monthly assessed according to RECIST as progressive disease (PD) or stable disease (SD). Immune response: pre and 20-day post treatment, Lymphocyte Proliferation Assay measured as thymidine-H3 incorporation (LPA) using peripheral blood mononuclear cells (PBMC) as responder cells and, as challengers: CEA, CA 15–3, AHD and 2 other autologous hemoderivatives (AH) obtained as AHD but from 2 lymphocyte populations (Wan Fal Ng preparation method): [CD4+CD25+] and [CD4+CD25-]. Results: After 8-month follow-up, 101 patients were evaluated (50/51 control/treated). Groups were comparable. In the treated group, 25/51 patients reached SD status, significantly higher (p<0.001) than in the controls (1/50 pts), and the responders (reaching SD) were 25 patients and non-responders (persisting PD) were 26. Post treatment, the responders have LPA positive (challenged > 4 x control) when their PBMCs were challenged with AHD, CEA, CA 15–3 (p<0.001) and AH from [CD4+CD25+] cells (p<002). LPA was negative before treatment and after treatment when challenger was AH from [CD4+CD25-] cells (p>0.5). Conclusions: AHD induced anti-progressive effect upon the tumor growth in 25/51 patients. This effect was associated with an immune response poli-targeted against molecules released from malignant cells to the blood (CEA/CA 15–3) and also against regulatory (tolerance) cells [CD4+CD25+] but not against [CD4+CD25-] cells. These facts are compatible with an anti-tumoral mechanism of autoimmunity elicited by AHD vaccine. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PharmaBlood
Predictors of oxaliplatin-induced peripheral neuropathy in patients with advanced colorectal cancer (CRC).
Authors: A. Y. Lin, N. B. Kouzminova
Journal: Journal of Clinical Oncology (2011)

619 Background: Chemotherapy-induced neuropathy (CINP) is one of the major dose-limiting toxicities of oxaliplatin. The purpose of this study was to identify early predictors of CIPN and investigate the feasibility of using nerve conduction studies (NCS) to monitor CINP. Methods: Under IRB-approved protocol, we systematically examined patient-reported symptoms, neurological tests and bilateral NCS of the peroneal, superficial peroneal and sural nerves every 3 weeks before each dose of oxaliplatin (75-130 mg/m 2 ) in 12 CRC patients receiving 8 to 13 cycles of XELOX. The severity of neuropathy was graded by the NCI Common Toxicity Criteria (CTC v.4.0) and the Oxaliplatin-Specific Neurotoxicity Scale (OSNS). Results: At the end of chemotherapy three of 12 patients developed peripheral sensory neuropathy CTC grade 3, five had grade 2, and four had grade 1 (3 of them had no self-reported symptoms with loss of Achilles tendon reflexes). At the eighth cycle test only 4 patients experienced CTC grade 2 criteria, but 7 of 12 patients had paresthesias persisting between the cycles of chemotherapy (OSNS grade 2 or higher). Development of grade 2 CINP by CTC or OSNS criteria by the eights cycle of chemotherapy was not associated with the total dose of oxaliplatin received (ANOVA p = 0.86 and 0.78 accordingly), but was significantly associated with administration of concomitant medication (Spearman correlation = 0.62, p = 0.03 for OSNS and 0.6, p = 0.04 for CTC grade 2 CINP). Presence of grade 2 or higher sensory neuropathy before the 8th cycle of oxaliplatin was significantly associated with development of grade 3 CINP by the time of chemotherapy completion (Spearman correlation = 0.8, p = 0.001). The maximal CINP grade that patients have reached during chemotherapy was also significantly associated with concomitant medication use (Spearman correlation = 0.76, p = 0.004). Conclusions: Concomitant administration of medications was the only factor significantly associated with severity of CINP in our study cohort. Further study is needed to verify if it is associated with altered bioavailability of oxaliplatin. No significant financial relationships to disclose.
Multidisciplinary Osteo-Oncology Center for the management of bone metastases
Authors: T. Ibrahim, L. Mercatali, P. Serra, R. Ricci, E. Flamini, L. Fabbri, R. Casadei, M. Falasconi, R. Galassi, O. Bazzocchi, D. Amadori
Journal: Journal of Clinical Oncology (2008)

20694 Background: Bone metastases are responsible for high morbidity in cancer patients. Multidisciplinary treatment is essential and should aim at decreasing the frequency of complications (pain, pathological fractures, spinal cord compression, bone marrow suppression and hypercalcemia), improving quality of life and prolonging survival. Methods: In January 2005 an Osteo-Oncology Center was opened in our Oncology Department. An oncologist coordinates a team of 18 specialists in palliative care, radiotherapy, orthopedics, nuclear medicine, radiology, physiatrics, histopathology and clinical pathology, with backup support from a biologist, data manager and nurse. A weekly multidisciplinary clinic is held and the facilitated, individually tailored diagnostic-therapeutic-care programs help to decrease waiting times and lessen psychophysical suffering. The weekly clinic appointments are divided into three phases: completion of questionnaires on pain and quality of life by patients, clinical evaluation by the multidisciplinary team (6 specialists), and anonymous patient completion of questionnaire on the quality of the service provided. Results: 392 patients (150 males and 242 females) were seen from January 2005 to December 2007. Reasons for referral to the Center were diagnostic doubts (25%), first diagnosis (10%), high risk of complications (35%), and unclassified (30%). A total of 583 multidisciplinary consultations were made. Sites of primary tumours were breast (37%), lung (11.5%), colon (4.3%), prostate (3.6%), stomach (3.1%), kidney (1.8%), and other tumors (38.7%). 56.8% of patients presented with pain at their first visit. 275 patients completed a questionnaire about pain and quality of life. Median pain intensity was 3.67 and pain treatment was changed in 127 patients. An anonymous questionnaire was also completed on the quality of the service provided: 76% of patients were very satisfied, 23% were fairly satisfied and only 1% expressed dissatisfaction. Conclusions: Our results highlight the usefulness of a multidisciplinary centre for the management of patients with bone metastases, especially in terms of preventing complications and decreasing psychophysical suffering of patients. No significant financial relationships to disclose.
Efficacy of a population-based colorectal cancer screening program and analysis of outcomes in screen-detected and non-screen-detected tumors.
Authors: David Mansouri, Donald C. Mcmillan, David S. Morrison, Emilia M. Crighton, Paul G. Horgan
Journal: Journal of Clinical Oncology (2014)

394 Background: Population based faecal occult blood test (FOBt) screening for colorectal cancer reduces cancer specific mortality through the detection of early stage disease. However, programmes are limited by uptake and the characteristics of the test itself. The aim of the present study was to compare features of screen detected (SD) and non-screen detected tumours (NSD) and assess the effect on cancer specific mortality. Methods: Prospectively maintained databases of both the prevalence round of a biennial population based FOBt screening programme and a regional cancer audit database were analysed. Mortality data was obtained from the national registry. Results: Of the 395,097 males and females aged 50 to 74yrs invited to screening, 203,886 (52%) responded, 6,085 (3%) tested positive and 4,632 (76%) attended for colonoscopy. A total of 951 patients were diagnosed with cancer within two years of screening invite: 378 (40%) SD and 573 (60%) NSD. Of the NSD patients, 376 (66%) were non-responders, 134 (23%) were FOBt negative and 63 (11%) did not attend or did not have cancer diagnosed at colonoscopy. Therefore, estimated FOBt sensitivity was 77%, and specificity was 99%. Comparing SD and NSD patients, SD patients were more likely to be male, less socioeconomically deprived, have a tumour with a lower Dukes stage, and more likely to have a left-sided tumour (all p&lt;0.05). In addition, SD patients were more likely to undergo an operation with a curative intent, less likely to undergo an emergency procedure, and less likely to die within 30 days of their procedure (all p&lt;0.001). With a median follow-up of 2 years, SD patients had improved cancer specific survival versus NSD patients (p&lt;0.001). This remained significant on multivariate survival analysis (Cox proportional hazards) including age, sex, deprivation, emergency presentation, tumour site and stage, and curative surgery (p&lt;0.001). Conclusions: Independent of established prognostic factors, SD patients have more favourable outcomes than those with NSD tumours. Therefore, further studies to improve the response rate to a screening invitation and the sensitivity of the current screening test are warranted.
Transcriptome Classification of B-Cell Non-Hodgkins Lymphoma.
Authors: Mohit Aggarwal, Raquel Villuendas, Fatima Al-Shahrour, Abel S. Aguilera, Nerea Martinez, Elena R. Ballesteros, Francisca I. Camacho, Alberto Perez, Maria J. Artiga, Jose A. Garcia-Marco, Joaquin Dopazo, Miguel A. Piris
Journal: Blood (2006)
Topiramate modulates post-infarction inflammation primarily by targeting monocytes or macrophages
Authors: Zhaohui Wang, Shiyuan Huang, Yuling Sheng, Xu Peng, Hui Liu, Nan Jin, Jun Cai, Yanwen Shu, Ting Li, Ping Li, Cheng Fan, Xiaofan Hu, Wenyong Zhang, Rui Long, Ya You, Caihong Huang, Yi Song, Chunhua Xiang, Jue Wang, Yong Yang, Kun Liu
Journal: Cardiovascular Research (2017)

Monocytes/macrophages response plays a key role in post-infarction inflammation that contributes greatly to post-infarction ventricular remodelling and cardiac rupture. Therapeutic targeting of the GABAA receptor, which is enriched in monocytes/macrophages but not expressed in the myocardium, may be possible after myocardial infarction (MI). After MI was induced by ligation of the coronary artery, C57BL/6 mice were intraperitoneally administered with one specific agonist or antagonist of the GABAA receptor (topiramate or bicuculline), in the setting of presence or depletion of monocytes/macrophages. Our data showed that within the first 2 weeks after MI, when monocytes/macrophages dominated, in contrast with bicuculline, topiramate treatment significantly reduced Ly-6Chigh monocyte numbers by regulating splenic monocytopoiesis and promoted foetal derived macrophages preservation and conversion of M1 to M2 or Ly-6Chigh to Ly-6Clow macrophage phenotype in the infarcted heart, though GABAAergic drugs failed to affect M1/M2 or Ly-6Chigh/Ly-6Clow macrophage polarization directly. Accordingly, pro-inflammatory activities mediated by M1 or Ly-6Chigh macrophages were decreased and reparative processes mediated by M2 or Ly-6Clow macrophages were augmented. As a result, post-infarction ventricular remodelling was attenuated, as reflected by reduced infarct size and increased collagen density within infarcts. Echocardiographic indices, mortality and rupture rates were reduced. After depletion of monocytes/macrophages by clodronate liposomes, GABAAergic drugs exhibited no effect on cardiac dysfunction and surrogate clinical outcomes. Control of the GABAA receptor activity in monocytes/macrophages can potently modulate post-infarction inflammation. Topiramate emerges as a promising drug, which may be feasible to translate for MI therapy in the future.
ボルテゾミブ+デキサメタゾンは,新たに診断された多発性骨髄腫における自家幹細胞移植に先立つ導入治療としてビンクリスチン+ドキソルビシン+デキサメタゾンより優れている: IFM 2005-01第III相試験の結果
Authors: Harousseau Jean-Luc, Attal Michel, Avet-Loiseau Herve, Marit Gerald, Caillot Denis, Mohty Mohamad, Lenain Pascal, Hulin Cyrille, Facon Thierry, Casassus Philippe, Michallet Mauricette, Maisonneuve Herve, Benboubker Lotfi, Maloisel Frederic, Petillon Marie-Odile, Webb Iain, Mathiot Claire, Moreau Philippe
Journal: Journal of Clinical Oncology (2010)
Can we improve on patient, caregiver, and family engagement for better outcomes?
Authors: Kenneth E Korber
Journal: Journal of Clinical Oncology (2016)

e289 Background: Use of multimedia characters have been a mainstay of commercial consumer marketing for decades; albeit to the detriment of healthy lifestyle and purchasing choices. Methods: We set out to change this paradigm by providing a socially-beneficial multimedia character concept as a community outreach engagement tool AND to provide a health champion for at-risk pediatric patient cohorts, their caregivers, and families. Results: A children's book series was written with the hypothesis that tested whether combining music and health would be a positive and measureable tool for audience engagement. A secondary goal was to create a platform wherenby this notion could be leveraged in multiple therapeutic areas and across multi-disciplinary professional groups. Conclusions: The Musical Adventures of Grace ((ISBN 978-1-68097-094-4) has been produced and is being integrated into two curricula: (i) a national music immersion education program for cognitive | neurophysiological | emotional wellness, and (ii) as a classroom-clinic longitudinal tool for elevating awareness of healthy living and reinforced choices in families at-risk for cardiovascular disease. This new model can be adapted to multiple challenges of childhood cancer nad will contribute to clinicians' communication armamentarium.
Family Camp: A multi-disciplinary intervention for brain tumor patients and families.
Authors: Margaretta S Page, Mary Lovely, Abigail Levinson Marks, Amanda K LaMarre, Susan M Chang, Jennifer Clarke, Judy Patt, Emelia Barani
Journal: Journal of Clinical Oncology (2016)

240 Background: The diagnosis of a brain tumor is a catastrophic life changing event that impacts the entire family. Patients and caregivers experience dramatic role changes, concern for their children, financial stress, and isolation. For many, the situation is overwhelming. A novel intervention to address these needs is “Family Camp”. Our vision for camp was to provide respite to the entire family, decrease caregiver stress, improve family connections and promote a sense of understanding and connection with the community at large. Methods: In a unique partnership with the widow of a former patient, the members of the UCSF Neuro-Oncology Division created and offered a weekend camp for brain tumor patients with children. Team members included MDs, RNs, social workers, psychologists, artists, body workers, “camp counselors” and community volunteers. In addition to respite, camp was structured through art, songs, projects and games to deliver opportunities for understanding and community building, including understanding the disease and its impact on the family. Therapeutic interventions included couples activities, counseling, parenting strategies, and providing a sense of connection to others dealing with brain tumors, the health care team, and camp volunteers. Anxiety, stress, depression, coping and values based living were measured pre and post camp using DASS21, CES-D, Brief Cope, Values Based Living instruments, and survey questions. Results: 11 families attended camp for 3 days in 2014. Improvement was noted in post camp testing of depression, anxiety and stress versus pre-camp. Survey questions showed the most common and important outcome to be connection, specifically that patients, caregivers, and children made connections with similar others. Families reported being able to relax and felt taken care of. They liked the opportunity for undistracted family time, getting to know their health providers outside of the office, and couples benefited from family counseling. Conclusions: Capitalizing on the unique skills of a multi-disciplinary team, one that includes the patient’s health care team, can lead to the delivery of a novel intervention that improves the illness experience of brain tumor patients and families.
Impact of an initial supportive oncology clinic visit on hospitalizations and emergency department visits.
Authors: Kimberly A. Curseen, Debbie Gunter, Gwendolynn Harrell, Lindsay Penny Prizer, Danielle Moulia, Tammie E. Quest
Journal: Journal of Clinical Oncology (2015)

150 Background: Hospitalizations and emergency department (ED) visits can be frequent, costly and discordant with stated goals-of-care for cancer patients. Little is known about the impact of outpatient palliative care and supportive oncology on hospitalizations and ED visits. Our aim was to investigate the impact of an initial visit at an outpatient supportive oncology clinic (SOC) on patient hospitalizations and ED visits. Methods: New patients were referred to a SOC from our health system’s oncologists from November 1, 2014 through January 31, 2015. Visits include a structured symptom assessment and personalized treatment plan from the clinic’s physician and/or nurse practitioner. Data were collected 90 days retrospectively and 90 days prospectively from 134 consecutive initial SOC visits. Descriptive statistics were calculated. We used the Wilcoxon signed rank test to compare the mean number of hospitalizations and ED visits in the 90 days prior and 90 days post a patient’s first SOC visit. Results: Mean patient age at first SOC visit was 55.6 (SD = 16.4). 51.2% of patients were female. The most common cancers were breast, lung, head and neck. Mean number of hospitalizations per patient was significantly (p &lt; 0.05) decreased: 1.3 (SD = 1.6) in the 90 days prior to initial SOC visit vs. 0.7 (SD = 0.7) in the 90 days post initial SOC visit. There was a non-significant reduction in mean ED visits per patient: 0.9 (SD = 0.9) in the 90 days prior to initial SOC visit vs. 0.7 (SD = 0.7) in the 90 days post initial SOC visit. Conclusions: Hospitalizations were significantly decreased and ED visits were reduced after the first visit to a small-scale SOC. This provides evidence that outpatient supportive care including aggressive symptom management may reduce patient crises, preventing ED visits and hospitalizations, and will likely lead to cost savings and improve quality of life for patients during and after cancer therapy. The decrease in hospitalizations and ED visits may be underestimated if disease was progressing and overestimated if disease was shrinking, but this data was not available for this study.