tbuckley/cabot-search huggingface dataset:
Tumor-specific peptide vaccination in newly-diagnosed patients with GBM
Authors: A. B. Heimberger, S. F. Hussain, K. Aldape, R. Sawaya, G. A. Archer, H. Friedman, D. Reardon, A. Friedman, D. Bigner, J. H. Sampson
Journal: Journal of Clinical Oncology (2006)

2529 Background: Despite multimodality approaches, survival with GBM is dismal. Induction of immune responses to suppress the infiltrative, residual component with an easily manufactured and administered immunotherapy has been a theoretical ideal. The epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific cell surface protein expressed on approximately 40% of GBMs. Methods: Newly-diagnosed GBM patients with a gross-total resection, a KPS ≥70, and EGFRvIII+, after undergoing radiation with concurrent temozolomide without tumor progression, were eligible to receive EGFRvIII peptide vaccination i.d. with GM-CSF. Primary endpoint was safety. Results: Accrual began in 06/14/2004 and is now complete. 19 patients were enrolled. Median follow-up is 18 months. Toxicity was minimal and without evidence of autoimmunity. Humoral and cellular immune responses were generated. Median TTP from surgery in vaccine-treated patients is 12 months (n = 12), comparing favorably with a historical matched unvaccinated cohort (gross total resection without progression during radiation, KPS≥70, EGFRvIII+) that had a median TTP of 7.1 months (n = 39) (p = 0.0058). These results also compared favorably with those reported for concurrent temozolomide and radiation followed by adjuvant temozolomide, with a median TTP of 6.9 months. Median survival in this trial has exceeded 18 months which compares favorably to all published analyses accounting for all known prognostic indicators. Among recurrent tumors evaluated by immunohistochemistry, 100% no longer expressed the EGFRvIII, suggesting immunological activation that eliminated EGFRvIII-expressing cells, as well as one potential mechanism of treatment failure. Conclusions: EGFRvIII peptide vaccination warrants further investigation in a larger randomized clinical trial in patients with EGFRvIII-expressing tumors. No significant financial relationships to disclose.
The Use of Bone Marrow Graft for Hematopoietic Stem Cell Transplantation From Matched Unrelated Donors After Reduced Intensity Conditioning Regimen Improves Survival : Analysis of the Societe Française De Greffe De Moelle Et De Therapie Cellulaire.
Authors: Andrea Toma, Marie-Lorraine Balère-Appert, Jean-Michel Boiron, Pierre Bordigoni, Gerard Socie, Jean-Paul Vernant, Marc Renaud, Noel Milpied, Mauricette Michallet, Eric Deconinck, Denis Guyotat, Frederic Garban, Anne Sirvent, Nathalie Contentin, Didier Blaise, Evelyne Marry, Agnes Buzyn
Journal: Blood (2009)
De-ESCALaTE: Comparison of early and late toxic events in low-risk HPV positive oropharyngeal carcinoma patients treated with chemoradiotherapy, cetuximab versus cisplatin.
Authors: Hisham Mohamed Mehanna, Christopher C McConkey, Andrew G. J. Hartley, M. Tessa Fulton-Lieuw, Joanne Grumett, Max Robinson, Bernadette Foran, Mehmet Sen, Anthony Kong, Janet Dunn
Journal: Journal of Clinical Oncology (2016)

TPS6103 Background: The rapid increase in oropharyngeal squamous cell carcinoma (OPSCC) incidence in the developed world has been attributed to a rise in Human Papillomavirus (HPV) infection. HPV related OPSCC is considered a distinct disease entity affecting a younger and healthier patient population. As such, acute and late toxicities, and the subsequent treatment strategy of those toxicities, have a significant impact on healthcare systems and societies, as well as patient lives. Standard platin-based chemoradiotherapy is associated with considerable acute toxicity and long term sequelae. De-ESCALaTE is a pragmatic, multi-centre, open label randomised clinical trial addressing the need to establish less toxic therapy in low-risk HPV positive head and neck cancer. Methods: Patients with low-risk HPV+ OPSCC are randomised to receive radiotherapy (70G in 35F) and either cisplatin (100 mg/m2 x 3) or cetuximab (400 mg/m2 loading dose followed by weekly 250 mg/m2) and will be followed up for two years. Patients who have a significant smoking history (i.e. more than 10 pack years) and advanced nodal status (i.e. N2b, N2c or N3) are excluded from this trial. The primary outcome measure is the total number of acute (occurring during treatment or up to 90 days after treatment) and late (occurring between 90 days and two years after treatment) severe or life threatening (Grades 3-5) events, which has been chosen because these events result in significant morbidity and a reduction would be considered beneficial by both patients and clinicians. The sample size calculation is based on the total number of toxicity events rather than the number of patients affected. This ensures that the risk of underestimation of the toxicity burden is minimised. Secondary outcomes are overall survival, quality of life and feeding tube use. Current enrolment into the De-ESCALaTE trial [ISRCTN number: ISRCTN33522080] is 239 randomised patients with a target total of 304 patients. The IDSMC last reviewed the trial in May 2015 and suggested that the trial continue as planned. Clinical trial information: ISRCTN33522080.
Advancement of Sialyltransferase Inhibitors: Therapeutic Challenges and Opportunities
Authors: Rémi Szabo, Danielle Skropeta
Journal: Medicinal Research Reviews (2016)

Abstract Hypersialylation of tumor cell surface proteins along with a marked upregulation of sialyltransferase (ST) activity is a well‐established hallmark of cancer. Due to the critical role of STs in tumor growth and progression, ST inhibition has emerged as a potential new antimetastatic strategy for a range of cancers including pancreatic and ovarian. Human STs are divided into subtypes based on their linkage and acceptor molecule, with each subtype controlling the synthesis of specific sialylated structures with unique biological roles. This has important implications for inhibitor development, as STs also play significant roles in immune responses, inflammation, viral infection, and neurological disorders. Thus, the current goal in order to advance to the clinic is the development of subtype selective, cell‐permeable and synthetically accessible, small‐molecule ST inhibitors. Herein is a comprehensive review of the latest developments in ST inhibitors from design, Nature, and high‐throughput screening, addressing both the challenges and opportunities in targeting cell surface sialylation. The review features an overview of the biological evaluation methods, computational and imaging tools, inhibitor molecular diversity, and selectivity toward ST subtypes, along with the emerging role of ST inhibitors as diagnostic tools for disease imaging.
Pegylated Liposomal Doxobubicin (PLD) Can Be Escalated in a Dose-Dense, 14 Day CDOP-Rituximab Regimen without Affecting Relative Dose Intensity (RDI) in Patients with Diffuse Large B Cell Lymphoma (DLBCL) Who Are Elderly or Have Compromised Cardiac Status.
Authors: Stephen J Noga, Judy Bosley, Pamela Nickoles, Pallavi Kumar, Erica Monfred
Journal: Blood (2009)
Outcomes in CCG-2961, a Children’s Cancer Group Phase III Trial for Untreated Acute Myeloid Leukemia (AML).
Authors: Beverly J. Lange, Franklin O. Smith, Patricia A. Dinndorf, Carola A.S. Arndt, Dorothy R. Barnard, Kathryn Dusenbery, Steven A. Feig, James H. Feusner, Sandra Luna-Fineman, Joseph Neglia, Nita L. Seibel, Leonard Sender, Kevin M. Shannon, Margie Weiman, Robert B. Gerbing, Todd A. Alonzo
Journal: Blood (2005)
The role of radiation therapy for multiple myeloma in the era of novel agents.
Authors: K. K. Abbi, H. Wagner, J. J. Drabick, T. P. Loughran, G. Talamo
Journal: Journal of Clinical Oncology (2010)

e18557 Background: Radiation therapy (RT) is one of the treatment modalities of multiple myeloma (MM), and it is commonly used in the treatment of pain, bone fractures, and spinal cord compression. We conducted a retrospective study of the use and clinical outcomes of RT in patients with MM diagnosed after the introduction of the three novel therapeutic agents: thalidomide, lenalidomide, and bortezomib. Methods: We retrospectively reviewed the medical records of 145 MM patients seen at the Penn State Hershey Cancer Institute in 2008. Results: Forty-six (32%) MM patients received RT, and 21 of them at more than one site, for a total number of 78 irradiated sites. The indications for local RT were palliation of bone pain (n= 49 sites), pathological fractures (n= 18), spinal cord compression (n= 7), and control of extramedullary disease (n= 4). The most common site of RT was the thoracic spine (18%). Spine and pelvis constituted together 53% of irradiation sites. RT was given within 6 months after the diagnosis of MM in 74% of cases, and at baseline (i.e., before starting systemic therapy) in 41% of cases. The mean number of stem cells collected for autologous transplantation was 12.6 x106 in 20 patients who received RT to spine and/or pelvis before the stem cell collection, and 26.2 x106 in 66 patients who did not, but the difference did not reach statistical significance (p=0.09). Conclusions: Despite the recent introduction of novel biological agents for the treatment of MM, RT continues to be a commonly utilized therapeutic strategy in the management of this disease. RT to spine and/or pelvis does not seem to significantly compromize the collection of peripheral blood stem cells for autologous transplantation. No significant financial relationships to disclose.
Physical activity programme reduces major disability in elderly people, study shows
Authors: Jacqui Wise
Journal: BMJ (2016)

Elderly people taking part in a structured physical activity programme were considerably less likely to experience impaired mobility than people who did not exercise regularly, a large study has shown.1

The study, published in Annals of Internal Medicine , followed up 1635 people aged 70-89 who were taking part in the Lifestyle Interventions and Independence for Elders (LIFE) programme at eight centres in the United States. At the start of the study all participants were sedentary but able to walk 400 m without help …
Impact of dose reduction on survival in patients starting sunitinib (SU) or pazopanib (PA) as first-line for metastatic renal cell carcinoma (mRCC).
Authors: Roberto Iacovelli, Lisa Derosa, Francesco Massari, Elena Verri, Luca Galli, Chiara Ciccarese, Maria Cossu Rocca, Claudia Cianci, Davide Bimbatti, Gaetano Aurilio, Andrea Antonuzzo, Emanuela Fantinel, Daniela Cullura, Sergio Ricci, Alessandra Modena, Alfredo Falcone, Giampaolo Tortora, Franco Nole
Journal: Journal of Clinical Oncology (2016)

553 Background: SU and PA are both VEGFR TKI approved for treatment of mRCC. Previous studies reported that the reduced dose (RD) is not recommended for the beginning of therapy (Motzer et al. 2012) and suggested a direct correlation between dose and effectiveness of therapy (Houk et al. 2010). We aim to investigate if patients (pts) that decreased the dose during treatment have different outcomes compared to those who continue a standard dose (SD). Methods: All pts affected by mRCC who started SU or PA at SD have been included. Pts were divided into two groups: RD and SD, based on whether they reduced the therapy or not. The main reasons for dose change have been collected and the RD group was defined into 2 levels (1st level: SU37.5mg/d, 4/2 or PA 600mg/d; 2nd level: SU25mg/d, 4/2 or PA 400mg/d). Pts were stratified by IMDC prognostic criteria and differences in pts’ characteristics between RD and SD groups were evaluated as well as median PFS and OS. Results: A total of 280 pts have been included. Median age was 62y and 68% was male; 54% had good prognosis, 40% intermediate and 6% poor. First-line was SU in 84% and PA in 16% of cases. A total of 123 (44%) pts decreased the dose to first- (89%) or second-level (11%). The main reasons were hand-foot syndrome (17.9%), diarrhea (15.4%) asthenia (14.6%), mucositis (13.0%) and thrombocytopenia (11.4%). Significant differences between RD and SD groups were the female sex (40% vs. 25%; p = 0.01) and the rate of primary refractory disease (11% vs. 31%: p &lt; 0.001). Median PFS and OS were 12.4 and 34.9 mos, respectively. In RD group, the median time before dose reduction was 3.5 mos. Excluding the primary refractory pts, median PFS was 18.6 and 15.0 mos (p = 0.06) and median OS was 68.0 and 40.7 mos (p = 0.14) in RD and SD group, respectively. In RD group, no differences between 1st- and 2nd-level of dose were observed both in PFS (11.0 vs. 13.1 mos; p = 0.82) and OS (42.8 vs. 36.0 mos; p = 0.78) after reduction. Conclusions: Dose reduction is a frequent event in pts who started a first-line therapy with SU or PA. This study reports that DR does not affect the survival of pts who initially started SU and PA at standard dose.
More resources are required to facilitate the discharge of acutely ill elderly people
Authors: S A Bruce, R R Lewis
Journal: BMJ (1995)

stay and bed use factor are better than the average for Wales, where most hospitals have parallel systems for admitting acute medical and geriatric emergencies.The appointment of a bed manager, flexible use of all acute beds in the hospital, and protocols for early discharge and transfer have failed to prevent constant overflows into non-medical wards, waits on trolleys in the accident and emergency department, and temporary closures, even though some general practices have access to community type hospital beds.Brief analysis (to be audited in more detail) suggests that few of the admissions are inappropriate.Major factors include patients' increased demands and expectations and general practitioners' fear of complaints and litigation.Given this, it is difficult to envisage any reduction in beds, let alone the 30% predicted in acute district general hospitals,3 whose surgeons are already practising day case surgery to a maximum.General practitioners have neither the time nor, probably, the skill needed to treat most of our acute medical admissions, even if they were provided with more facilities.Planning must be modified to take account of these issues.
Long-term clinical outcomes of ‘Prairie Epidemic Strain’<i>Pseudomonas aeruginosa</i>infection in adults with cystic fibrosis
Authors: Ranjani Somayaji, John C Lam, Michael G Surette, Barbara Waddell, Harvey R Rabin, Christopher D Sibley, Swathi Purighalla, Michael D Parkins
Journal: Thorax (2016)

Epidemic Pseudomonas aeruginosa (PA) plays an important role in cystic fibrosis (CF) lung disease. A novel strain, the 'Prairie Epidemic Strain' (PES), has been identified in up to 30% of patients in Prairie-based Canadian CF centres.To determine the incidence, prevalence and long-term clinical impact of PES infection.A cohort of adults with CF was followed from 1980 to 2014 where bacteria isolated from clinical encounters were prospectively collected. Strain typing was performed using pulse-field gel electrophoresis and multilocus sequence typing. Patients were divided into one of four cohorts: no PA, transient PA, chronic PA with unique strains and chronic PES. Proportional Cox hazard and linear mixed models were used to assess for CF-associated respiratory death or transplantation, and rates of %FEV1 and body mass index (BMI) decline.274 patients (51.7% male) were analysed: 44--no PA, 29--transient PA, 137--unique PA, 64--PES. A total of 92 patients (33.6%) died or underwent lung transplantation (2423.0 patient-years). PES infection was associated with greater risk of respiratory death or lung transplant compared with the no PA group (aHR, 3.94 (95% CI 1.18 to 13.1); p=0.03) and unique PA group (aHR, 1.75 (95% CI 1.05 to 2.92) p=0.03). Rate of lung function decline (%FEV1 predicted) was greatest in the PES group (1.73%/year (95% CI 1.63% to 1.82%); p<0.001). BMI improved over time but at an attenuated rate in the PES group (p=0.001).Infection with PES was associated with increased patient morbidity through three decades and manifested in an increased risk of respiratory death and/or lung transplantation.
Release of extracellular DNA influences renal ischemia reperfusion injury by platelet activation and formation of neutrophil extracellular traps
Authors: Marcel P.B. Jansen, Diba Emal, Gwendoline J.D. Teske, Mark C. Dessing, Sandrine Florquin, Joris J.T.H. Roelofs
Journal: Kidney International (2016)
Utility of the of the M. D. Anderson Symptom Assessment Inventory (MDASI) for symptom evaluation during chemoradiation (CRT) in patients with gastrointestinal malignancies
Authors: N. A. Janjan, X. S. Wang, T. Mendoza, Y. Zhang, P. Das, C. Crane, M. Delclos, S. Krishnan, C. Cleeland
Journal: Journal of Clinical Oncology (2007)

6613 Background: Symptom assessment has become an important therapeutic endpoint in clinical trials. Measures that evaluate symptoms during CRT are needed for evaluation of clinical benefit in developing therapeutics and in monitoring quality improvement in clinical practice. Methods: 330 patients with gastrointestinal malignancies (Liver/Biliary:44; Colon:45; Rectal:197; Gastric:44) were evaluated during CRT with the self-reported MDASI-GI. All patients received 45–56Gy of radiation (1.8Gy/fraction); 78% received between 45–50.4Gy. In all cases fluoropyrimidine (oral or intravenous) was given concurrently during radiation. Lowess curves were used to describe the severity and pattern of each symptom evaluated. ANOVA was used to compare the mean severity of symptoms by tumor type. Follow-up evaluations were performed with a t-test using a Bonferroni corrected level of significance [p&lt; 0.002]. Results: Relationships among symptoms were examined using 1,020 symptom measurements (Liver/Biliary:141; Colon:132; Rectal:613; Gastric:134 observations). Lowess curves showed almost parallel steep increases in pain and poor appetite between weeks 2–4 of CRT. Fatigue was most profound in Liver/Biliary and Rectal cancers. As expected, no significant differences in dyspnea were found among these cancers. CRT for Rectal cancer produced the worst symptom burden with significantly more pain, skin pain, and diarrhea. Consistent with clinical findings, poor appetite, nausea and vomiting were statistically more common during CRT for Gastric cancer. Conclusions: The MDASI is a brief and easy to use symptom measure in the clinical setting and is sensitive to treatment-related symptom changes during CRT in abdominopelvic malignancies. [Table: see text]
Managing back pain and osteoarthritis without paracetamol
Authors: Christian Mallen, Elaine Hay
Journal: British Journal of Sports Medicine (2016)

Paracetamol (acetaminophen) is a drug we are all familiar with. It is cheap, readily available over the counter, and is common place in family medicine cabinets across the world. We rely on it in the middle of the night to settle childhood fevers, and it is usually our first choice drug for a wide range of painful musculoskeletal disorders, including osteoarthritis and spinal pain. Yet new evidence in a linked paper by Machado and colleagues (doi:10.1136/bmj.h1225) casts doubt on the efficacy and safety of paracetamol and questions its place as our first choice analgesic.1

In their systematic review and meta-analysis examining the efficacy and safety of paracetamol for spinal pain and osteoarthritis, Machado and colleagues synthesised evidence from 13 randomised controlled trials.1 They report that there is “high quality” evidence that paracetamol is ineffective for reducing pain intensity and disability in patients with low back pain and “high quality” evidence that paracetamol produces a significant but not clinically important effect on pain and disability in patients with osteoarthritis. While adverse events were reported at a similar level …
A phase II study of pemetrexed and gemcitabine plus bevacizumab as first-line chemotherapy for elderly patients with stage IIIb/IV non-small cell lung cancer.
Authors: L. Blakely, L. S. Schwartzberg, F. M. Schnell, K. D. Sabbath, P. J. Miller, E. J. Stepanski
Journal: Journal of Clinical Oncology (2010)

e18023 Background: A previous phase II study of pemetrexed (PEM) and gemcitabine (GEM) in combination in elderly patients showed significant activity with little toxicity. Adding VGFR inhibitors to active doublets has increased response rates in patients with non-small cell lung cancer (NSCLC) in previous studies. The present study evaluated the doublet of PEM and GEM with bevacizumab (BEV). Methods: 48 patients with histologically proven stage IIIB or IV NSCLC were enrolled. All patients received PEM 500 mg/m2 with GEM 1,500 mg/m2 plus BEV 10 mg/kg. All medications were given day 1 of each two week cycle. Patients were given vitamin B12 injection and folic acid 400 mg daily at least 5 days before initiating therapy. Results: Gender of enrolled patients was male = 27 (56.3%) and female = 21 (43.8%). Median age of enrolled patients was 72 (range 65-84). Patients with stage IV disease = 43 (89.6%), and patients with stage IIIB disease = 5 (10.4%). 42 pts had an adenocarcinoma (87.5%), and 4 (8.3%) pts had a large cell carcinoma. 17 patients were ECOG = 0 (35.4%) while 30 patients were ECOG = 1 (62.5%). Best overall response for 45 patients who have completed the study was: PR, 21 (46.7%), SD, 15 (33.3%), PD, 6 (13.3%), and not evaluable, 3 (6.7%). Median PFS in 47 evaluable patients was 6.88 months. The median overall survival (OS) was 8.78 months. The most common hematological toxicity was neutropenia, occurring in 30 (62.5%) patients (severity = G3- 5 pts/10%; G4- 9 pts/19%). Fatigue and weight/appetite changes were the most common non-hematological toxicities, each occurring in 40 (83%) patients, but were low severity (no G4 for either; fatigue G3 = 10%; appetite/weight G3 = 8%). Conclusions: The PFS and overall response rate were better than that seen in studies with a platinum doublet alone. However, OS was lower, and this may be due to the age of the patients in this study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Lilly