tbuckley/cabot-search huggingface dataset:
Regorafenib (REG) in the real-life setting: First results from a large French compassionate-use program in patients (pts) with previously treated metastatic colorectal cancer (mCRC).
Authors: Antoine Adenis, Louis-Marie Dourthe, Laurent Mineur, David Tougeron, Christophe Tournigand, Pierre-Luc Etienne, Bernard Paule, Philippe Laplaige, Emmanuelle Tresch, Jean-François Morère, Antoine Hollebecque, Aurelie Ferru, Françoise Desseigne, David Malka, Pierre Michel, Pierre Arvis, Stephanie Clisant, Jean Marc Phelip, Christelle De La Fouchardiere, Thierry André
Journal: Journal of Clinical Oncology (2014)

e14599 Background: Regorafenib (REG) is an oral multikinase inhibitor with survival benefits in patients (pts) with pretreated metastatic colorectal cancer (mCRC). The Temporary Authorization for Use (ATU) is an exceptional procedure approved by the French National Agency of Medicine and Health Products Safety to provide early access to new medicinal products, especially for pts with unmet medical need. Prescribing conditions, based on the ATU label, are less stringent than selection criteria in clinical trials. The collection of ATU data contributes to a better understanding of the medicinal product in the real-life setting. Methods: REG was made available for ATU in the treatment of adult pts with mCRC who have failed, or are not considered candidates for, fluoropyrimidine-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy, and, if pts were KRAS wild type, an anti-epidermal growth factor receptor (EGFR) therapy. Pts were treated and monitored according to criteria fully defined in a protocol for therapeutic use and information collection. Descriptive analyses of baseline characteristics of pts were conducted on an intent-to-treat basis. Results: From December 2012 to October 2013, 1,178 pts met the ATU criteria, of whom 1,119 started on REG. Pts were treated in 310 institutions by 541 different physicians. The median number of pts treated by each physician was two (range 1-13). 681/1178 (57.8%) were male. Median age was 64 years (range 25-92). Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 (30.9%), 1 (59.2%), 2 (9.3%), and 3 (0.5%). Median time since diagnosis of the metastatic disease was 2.7 years. KRAS mutation was documented in 604/1178 (51.3%) of pts. Metastases were predominantly located in the liver (76.0%) and lungs (62.1%). Previous therapies included a fluoropyrimidine (99.5%), irinotecan (99.2%), oxaliplatin (98.0%), bevacizumab (91.5%), cetuximab, and/or panitumumab (48.1%). The starting dose of REG was 160 mg/day in 89.7% of patients. Conclusions: Apart from a reported baseline PS>1 in 10% of the pts, the patterns of pts included in the ATU seem to be comparable to those of pts included in the pivotal phase III CORRECT study. Further analyses are in progress to explore actual treatment characteristics, safety, and efficacy of regorafenib in this real-life setting.
Chemotherapy in the intensive care unit patient: A friend or a foe?
Authors: Ludhmila A Hajjar, Clarice H Park, Julia Tizue Fukushima, Juliano Almeida, Eduardo A Osawa, Rosana Nakamura, Danielle Nagaoka, Filomena Galas, Maria Del Pilar Estevez-Diz
Journal: Journal of Clinical Oncology (2014)

e20722 Background: Over the last years, advances in cancer treatment resulted in increased rates of intensive care unit (ICU) admission. In many cases, due to extensive disease and related complications, chemotherapy is prescribed during ICU stay in critically ill cancer patients. The aim of this study is to describe a series of patients undergoing chemotherapy in ICU, with attention to mortality risk factors. Methods: From August 2012 to December 2013, 2300 patients were admitted to the ICU of Cancer Institute of State of Sao Paulo, a 84-bed ICU of a tertiary referral center linked to University of Sao Paulo. Medical records were retrospectively reviewed and a phone call was performed to each individual patient to assess the 12-month mortality. Results: A total of 38 patients received chemotherapy and were included in the study. The mean age was 47 years (SD 16). There were 15 (39%) patients with nonhematological malignancy and 23 (61%) with hematologic malignancy. Most patients had localized disease (79%) and 53% of patients have received previous chemotherapy (53%). Septic shock was the main cause of admission, diagnosed in 27 patients (71%). Hospital mortality was 68% and one-year mortality was 71%. Most patients received chemotherapy in the first 72 hours of ICU admission (55%). The most frequently prescribed chemotherapy drug was doxorubicin. An univariate analysis showed that among non-survivors, the incidence of septic shock as cause of admission was significantly higher when compared to survivors (85% vs. 14%, p=.001). Also, non-survivors had a higher incidence of cardiovascular dysfunction (days on vasoactive drugs 13 vs. 0, p=.003) and spent more days on mechanical ventilation (2 vs. 0, p=.015). Of the patients with a diagnosis of septic shock who received chemotherapy, 85% died in the hospital as compared to 27% of mortality in patients without septic shock. Conclusions: Chemotherapy in the ICUs is usually prescribed in high risk patients with life-threatening disease. However, in the subgroup admitted for septic shock with respiratory or cardiovascular dysfunctions, chemotherapy was associated with increased mortality.
Mitoxantrone, Etoposide and Cytarabine (MEC) Can Induce Deep Complete Remission and Is an Effective Bridge Therapy to Allotransplantation (SCT) in Refractory/Relapsed Acute Myeloid Leukemia (AML) Patients
Authors: Giovanni Marconi, Annalisa Talami, Maria Chiara Abbenante, Stefania Paolini, Chiara Sartor, Sarah Parisi, Stefano de Polo, Jacopo Nanni, Luca Bertamini, Simone Ragaini, Matteo Olivi, Maria Chiara Fontana, Maria Teresa Bochicchio, Emanuela Ottaviani, Carmen Baldazzi, Nicoletta Testoni, Giovanni Martinelli, Michele Cavo, Cristina Papayannidis, Antonio Curti
Journal: Blood (2018)
Cabozantinib (Cabo) in patients (pts) with castrate-resistant prostate cancer (CRPC) metastatic to bone (NCT01428219): Evaluation of bone metastasis microenvironment.
Authors: Petros Grivas, Stephanie Daignault, Kathleen A. Cooney, Jon Jacobson, Corrie Yablon, Brian Dale Ross, Thomas L Chenevert, Ben Hoff, Alnawaz Rehemtulla, Evan T. Keller, Rohit Mehra, Greg Shelley, Ajjai Shivaram Alva, Maha Hussain, David C Smith
Journal: Journal of Clinical Oncology (2014)

e16015 Background: Cabo is active in metastatic CRPC. This phase II trial evaluates the effects of Cabo on bone metabolism and tumor activity in prostate cancer bone lesions. Methods: Chemotherapy-naive pts with progressive CRPC and bone metastases accessible to CT-guided biopsy, adequate performance status/organ function underwent bone biopsy, CT and perfusion/diffusion-weighted MRI of bone lesions at baseline and after 6 weeks of Cabo 60 mg daily. Primary endpoint: rate of pts progression-free at 12 weeks (PF12w). Secondary endpoints: safety, PF survival, response proportion/duration, PSA response/time-to-progression. Exploratory endpoints: serum markers of bone metabolism, imaging of bone lesions, immunohistochemistry (IHC) of bone biopsies. A two-stage mini-max design permits early termination after the first 27 evaluable pts (≤12 pts PF12w); alternatively 46 evaluable pts will be accrued with 85% power to detect a PF12w rate <0.45 or >0.65 (5% type I error). Results: 26 pts have been screened, 23 enrolled, 21 started Cabo (8 pts still on Cabo, 6 of them >12 weeks). Median age is 65, median baseline PSA 50.1 ng/ml, median treatment duration 28 (3-88) weeks with 25 dose delays in 15 pts and 18 dose reductions in 14 pts. Grade (G) 3 adverse events (AE) >5%: thromboembolism (14%), elevated lipase (14%), diarrhea (9.5%), no G4/5 AE on Cabo. 14/19 (74%) pts were PF12w; 1 pt had unconfirmed partial response by CT; 6/19 (32%) pts had PSA response, 5/19 (26%) pts had bone scan response (1 complete). Bone biopsy tumor yield was 36% on preliminary analysis; Met, Akt, VEGFR2 IHC and serum markers evaluation is underway. 14 pts had paired MRI data:13 pts PF12w had increased tumor mean apparent diffusion coefficient (ADC) and volume fractions of parametric response map of ADC (PRM_ADC)+ between MRI images; 1 pt not PF12w had insubstantial mean ADC change and the lowest PRM_ADC+ fraction. PRM analysis on Hounsfield Units between CT scans in 13 pts did not reveal substantial bone changes. Conclusions: Based on achieving the primary endpoint of the first stage, study accrual continues. Analysis of biopsy specimens, tumor imaging and bone markers is ongoing. Clinical trial information: NCT01428219.
Intensive Induction Regimens after Deferring Initial Therapy Are Not Associated with Improved Progression-Free or Overall Survival in Patients with Mantle Cell Lymphoma (MCL)
Authors: Krithika Shanmugasundaram, Subir Goyal, Jeffrey M. Switchenko, Oscar Calzada, Michael C Churnetski, Bhaskar Kolla, Veronika Bachanova, James Nathan Gerson, Stefan Klaus Barta, Max J. Gordon, Alexey V Danilov, Natalie S Grover, Stephanie Mathews, Madelyn Burkart, Reem Karmali, Yazeed Sawalha, Brian T. Hill, Nilanjan Ghosh, Steven I Park, Narendranath Epperla, David A. Bond, Talha Badar, Kristie A. Blum, Mehdi Hamadani, Timothy S. Fenske, Mary Malacek, Brad S. Kahl, Christopher R Flowers, Jonathon B. Cohen
Journal: Blood (2018)
FRI0656 Predictive validity of presenteeism measures with dual answer keys in inflammatory arthritis
Authors: M. Donaldson, A. Kobza, D. E. Beaton, H. Xie, E. C. Sayre, M. A. M. Gignac, D. Lacaille
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Employment studies in arthritis have emphasized the importance of decreased productivity at work, or presenteeism. However, consensus is still lacking on how to best measure this construct. Instruments used include the Work Limitations Questionnaire (WLQ), which measures the amount of time people are limited, and the Workplace Activity Limitations Scale (WALS), which measures the degree of difficulty. We modified the response keys of the WLQ and WALS, creating a dual answer key assessing both degree of difficulty and amount of time with difficulty. Previous work by our group has shown that scores obtained from combining responses to the dual answer keys exhibit good internal consistency, criterion and construct validity. <h3>Objectives:</h3> The objective of this study was to evaluate the ability of the combined scores to predict future work cessation and number of work days missed due to arthritis. <h3>Methods:</h3> A longitudinal study used baseline and 6-month data from the RCT of an employment intervention, the "Making It Work" Program. Inclusion criteria were: inflammatory arthritis, age 19–59, working at baseline, and concerns about arthritis affecting work. 327 participants were included (RA:173, PsA:48, SLE:42, AS:64). Combined scores were obtained by i) multiplying, and ii) adding, the scores of difficulty and time answer keys at the item level. We assessed the predictive ability of the combined scores, and the original scores, of the WALS and WLQ to predict work cessation due to arthritis within 6 months using binary logistic regression models, or number of work days missed due to arthritis using zero-inflated Poisson models. <h3>Results:</h3> WLQ and WALS original and combined scores were significant predictors of future work cessation and number of work days missed. The WLQ combined scores predicted work cessation better than the original score (AIC:117.6 &amp; 118.2 for multiplicative and additive combinations, respectively vs. 125.4 for time) and work days missed (AIC:2179.8 &amp; 2177.8 vs. 2188.7). WALS original score (ie. degree of difficulty) predicted work cessation better than combined scores (AIC:95.8 vs. 109.3 &amp; 109.4). However, WALS combined scores predicted number of work days missed better (AIC:1696.9 &amp; 1673.4 vs. 1795.2). <h3>Conclusions:</h3> Combined scores from dual answer keys applied to the WLQ and WALS significantly predicted future work cessation and number of work days missed. Using combined scores, rather than original answer keys, improved the ability of the WLQ to predict both work cessation and work days missed, but only improved the ability of the WALS to predict work days missed. <h3>Disclosure of Interest:</h3> None declared
Abstract 13734: Assertive Call-Taking Increases the Provision of Telephone Cardiopulmonary Resuscitation During Out-of-Hospital Cardiac Arrest
Authors: Amy S Capone, William M Munion, Micah Panczyk, Vatsal Chikani, Daniel W Spaite, Tyler F Vadeboncoeur, Shikira Suell, Taylor A George, Terry Mullins, Bentley J Bobrow
Journal: Circulation (2017)

Background: Telephone cardiopulmonary resuscitation (TCPR) is associated with improved outcomes after out-of-hospital cardiac arrest (OHCA). AHA guidelines recommend that 9-1-1 call takers (CTs) as...
The G-protein coupled receptor ChemR23 determines smooth muscle cell phenotypic switching to enhance high phosphate-induced vascular calcification
Authors: Miguel Carracedo, Gonzalo Artiach, Anna Witasp, Joan Clària, Mattias Carlström, Andres Laguna-Fernandez, Peter Stenvinkel, Magnus Bäck
Journal: Cardiovascular Research (2018)

Abstract Aims Vascular calcification, a marker of increased cardiovascular risk, is an active process orchestrated by smooth muscle cells. Observational studies indicate that omega-3 fatty acids protect against vascular calcification, but the mechanisms are unknown. The G-protein coupled receptor ChemR23 transduces the resolution of inflammation induced by the omega-3-derived lipid mediator resolvin E1. ChemR23 also contributes to osteoblastic differentiation of stem cells and bone formation, but its role in vascular calcification is unknown. The aim of this study was to establish the role of ChemR23 in smooth muscle cell fate and calcification Methods and results Gene expression analysis in epigastric arteries derived from patients with chronic kidney disease and vascular calcification revealed that ChemR23 mRNA levels predicted a synthetic smooth muscle cell phenotype. Genetic deletion of ChemR23 in mice prevented smooth muscle cell de-differentiation. ChemR23-deficient smooth muscle cells maintained a non-synthetic phenotype and exhibited resistance to phosphate-induced calcification. Moreover, ChemR23-deficient mice were protected against vitamin D3-induced vascular calcification. Resolvin E1 inhibited smooth muscle cell calcification through ChemR23. Introduction of the Caenorhabditis elegans Fat1 transgene, leading to an endogenous omega-3 fatty acid synthesis and hence increased substrate for resolvin E1 formation, significantly diminished the differences in phosphate-induced calcification between ChemR23+/+ and ChemR23−/− mice. Conclusion This study identifies ChemR23 as a previously unrecognized determinant of synthetic and osteoblastic smooth muscle cell phenotype, favouring phosphate-induced vascular calcification. This effect may be of particular importance in the absence of ChemR23 ligands, such as resolvin E1, which acts as a calcification inhibitor under hyperphosphatic conditions.
Rechallenge with anti-EGFR–based therapy in metastatic colorectal cancer: Impact of intervening time interval and prior anti-EGFR response.
Authors: Xiaochun Liu, Goldy C. George, Apostolia Maria Tsimberidou, Aung Naing, Jennifer J. Wheler, Scott Kopetz, Siqing Fu, Sarina Anne Piha-Paul, Cathy Eng, Gerald Steven Falchook, Filip Janku, Chris R. Garrett, Daniel D. Karp, Razelle Kurzrock, Ralph Zinner, Kanwal Pratap Singh Raghav, Vivek Subbiah, Funda Meric-Bernstam, David S. Hong, Michael J. Overman
Journal: Journal of Clinical Oncology (2014)

3607 Background: This retrospective study aims to investigate the activity of retreatment with anti-EGFR-based therapy in order to explore the concept of clonal evolution by evaluating the impact of prior activity and intervening time interval. Methods: One hundred and four KRAS-wild-type metastatic colorectal patients (pts) were re-treated on phase I or I/II clinical trials containing anti-EGFR therapy after progressing on prior cetuximab or panitumumab. Physician-recorded response (CR, PR, SD >=6 months) were used for prior treatment evaluation, and the best response per RECIST criteria were used for the re-treatment evaluation. The multivariate analysis was constructed with response on prior treatment, interval time between the two treatments, age, race, gender, Royal Marsden Hospital prognostic score, and performance status. Results: Pt characteristics were: 72% Caucasian, 66% < 60 years of age, 51% female gender, median PS 1, 84% normal albumin, and 76% elevated LDH levels. Re-treatment anti-EGFR agents were cetuximab (n=89) or cetuximab plus erlotinib (n=15). The median interval time between prior and re-treatment was 4.55 months (range: 0.46-58.7). Pts who responded to the prior cetuximab or panitumumab were more likely to respond to the re-treatment compared to the non-responders in both univariate (p = 0.005) and multivariate analyses (OR: 3.45, 95% CI: 1.35, 8.85, p = 0.01). The response rate in re-treatment also correlated with interval time between the two anti-EGFR based therapies (p = 0.044). Moreover, median PFS on re-treatment was marginally increased in prior responders (4.37 months, 95% CI: 2.92, 5.82) compared to prior non-responders (2.37 months, 95% CI, 1.52, 3.22) in univariate (p = 0.056) and multivariate analysis (HR: 0.67, 95% CI: 0.42-1.08, p = 0.101). Conclusions: Our data supports the concept of clonal evolution though the impact appears less robust than previously reported (Santini et al. 2012). Further work to validate which pts benefit from re-challenge treatment post progression is needed.
Impact of marital status on survival among patients with cholangiocarcinoma.
Authors: Eesha Sasumana, Madhuri Reddy Nooka
Journal: Journal of Clinical Oncology (2014)

e17698 Background: Cholangiocarcinoma (CC) is the 2nd most common primary hepatobiliary tumor. The incidence of CC in US is steadily increasing over the last few decades. CC is known to affect elderly patients and with prior studies confirming marital status as an independent predictor of overall survival (OS) in elderly cancer patients, we undertook the analysis to evaluate the impact of marital status on OS of CC patients. Methods: Patients with diagnosis of CC (International Classification of Diseases for Oncology, 3rd Edition code 8160/3, 8161/3 and 8162/3) were identified in the SEER database consisting of 18 registries. First, we have evaluated the age-adjusted incidence by age groups to test the hypothesis that CC is a disease of elderly. Second, we sought to evaluate the impact of marital status on OS by age categorization at diagnosis (15-44, 45-54, 55-64, 65-74, 75-84 and 85+ years). Rates are per 100,000 and age-adjusted to the 2000 US standard population. Results: In all, 15107 cases of CC were identified. The age-adjusted rate of CC for patients aged 20-24years is 0.006 compared to 4.42 for 65-69 and 10.47 for 85+ years, respectively. Among all CC patients, 54.9% were married, 22.5% widowed and 22.6% others (10.9% single, 7.7% divorced, 0.9% single and 3.1% unknown). Median age of diagnosis is 70 years in males and 73 in females. Among all patients, OS from the time of diagnosis was 4 months. Among patients that are married, OS is 6 months (95% confidence interval (CI) 5.72-6.28), compared to 3 months in others (95% CI 2.80-3.20). By age group, married vs others by age groups 15-44 were (10 months vs. 8 months; p=0.68), 45-54(10 months vs. 7 months; p=0.004), 55-64 (8 months vs. 5 months; p=0.000), 65-74 (6 months vs. 4 months; p=0.000), 75-84 (4 months vs. 3 months; p=0.001) and 85+ years (2 months vs. 2 months; p=0.038). Conclusions: The sloping trend of age-adjusted ratios supports the hypothesis that the incidence of CC increases linearly with age confirming this is a disease of elderly. The median age at time of diagnosis confirms it. In patients with CC, except in younger patients aged 15-44 years, married status which is a surrogate for a healthy support system improves survival among all other age groups with cholangiocarcinoma.
Impact of 18F FDG PET/CT on staging of non-small cell lung cancer.
Authors: Chetsadaporn Promteangtrong, Anchisa Kunawudhi, Rossarin Phadungrerk, Chanidapa Iamsa-art, Chanisa Chotipanich
Journal: Journal of Clinical Oncology (2014)

e22105 Background: The best option for treatment of non-small cell lung cancer (NSCLC) depends on optimal initial staging. FDG PET/CT could play an important role for staging of NSCLC by reducing the number of futile operations. However, FDG PET/CT is a relatively expensive modality. Particularly, Thai reimbursement policy at present does not cover FDG PET/CT for staging of NSCLC. This study aimed to evaluate the clinical impact of FDG PET/CT in the management of Thai patients with NSCLC. Methods: A prospective study was conducted in 17 patients with lung mass and histopathology confirmation of NSCLC (2 squamous cell carcinoma and 15 adenocarcinoma). All patients underwent FDG PET/CT, during July – December 2013, for initial staging. PET/CT results were analyzed visually by 2 independent nuclear medicine physicians. Most preferable and distinctive treatment options (local curative treatment, neoadjuvant treatment or palliation) during pre- and post-FDG PET/CT were identified for each patient. The changes in management decisions of pre- and post- FDG PET/CT were assessed. Results: Four patients with stage IA, 2 patients with stage IB, 1 patient with IIB, 1 patient with stage IIIA and 9 patients with stage IV as defined by conventional assessment. FDG PET/CT upstaged in 5/17 patients (29.4%) and gave a false negative result in 1 patient. Of the former 5 patients, stage was changed from IA, IA, IA, IIB and IIIA to be IIIA, IV, IB, IV and IV, respectively. Management decisions were changed in 4 patients and remained unchanged in 1 patient. For 4 patients with changing management, treatment altered from local curative treatment to palliation in 2 patients, neoadjuvant treatment to palliation in 1 patient and adjunct mediastinoscopy with biopsy before local curative treatment in 1 patient. FDG PET/CT showed unsuspected distant metastases in brain, adrenal gland, bone and muscle. One of the 17 patients had incidental finding of increased FDG uptake in the ascending colon with biopsy-confirmed as low grade tubular adenoma. Conclusions: Our data suggested an important role of FDG PET/CT in staging of NSCLC. Additional PET/CT information may influence therapeutic options and reduce unnecessary surgery in patients with metastatic disease.