tbuckley/cabot-search huggingface dataset:
Chemotherapy With or Without Anti-EGFR Agents in Left- and Right-Sided Metastatic Colorectal Cancer: An Updated Meta-Analysis
Authors: Zi-Xian Wang, Hao-Xiang Wu, Ming-Ming He, Ying-Nan Wang, Hui-Yan Luo, Pei-Rong Ding, Dan Xie, Gong Chen, Yu-Hong Li, Feng Wang, Rui-Hua Xu
Journal: Journal of the National Comprehensive Cancer Network (2019)

Abstract Background: Previous meta-analyses have suggested primary tumor location as a predictive factor for efficacy of anti–epidermal growth factor receptor (EGFR) therapies in patients with metastatic colorectal cancer (mCRC). However, the recent phase III TAILOR trial addressing this issue was not included in those analyses. This meta-analysis incorporated data from the TAILOR trial to evaluate the efficacy of chemotherapy plus anti-EGFR agents (cetuximab [Cet] or panitumumab [Pani]) versus chemotherapy alone for RAS wild-type (wt) right- and left-sided mCRC. Patients and Methods: A PubMed-based literature search was conducted to identify randomized controlled trials (RCTs) studying the additional efficacy of Cet/Pani in combination with chemotherapy versus chemotherapy alone in RAS wt left- and right-sided mCRC. Study-level pooled analyses of hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for objective response rate (ORR) were performed. Results: Three first-line RCTs (CRYSTAL, PRIME, and TAILOR) and one second-line RCT (20050181) were included. Significant OS benefits from Cet/Pani were observed in the left-sided (HR, 0.76; 95% CI, 0.66–0.86) but not right-sided subgroups (HR, 0.99; 95% CI, 0.78–1.27). However, the addition of Cet/Pani to chemotherapy significantly improved PFS and ORR in both the left-sided (HR, 0.70; 95% CI, 0.57–0.86, and OR, 3.28; 95% CI, 1.95–5.51, respectively) and right-sided subgroups (HR, 0.76; 95% CI, 0.59–0.99, and OR, 1.78; 95% CI, 1.08–2.93, respectively). Conclusions: The addition of Cet/Pani to chemotherapy significantly benefits PFS and ORR in patients with RAS wt right-sided mCRC, indicating that anti-EGFR therapies may remain an option for selected patients.
Simultaneous care in Italy’s Veneto Region Health District 8: Integrated assistance to provide better outcomes in end-of-life care.
Authors: Fabio Girardi, Paola Paiusco, Paolo Manente, Michela Bortolin, Maria Grazia Ruggeri, Antonella Biancon, Giovanni Vicario, Elvira Scelzi, Gigliola Sgarbossa, Costanza De Rossi, Giuseppe Vultaggio, Giuseppe Mazzola
Journal: Journal of Clinical Oncology (2012)

e19595 Background: The number of cancer patients requiring active treatment and palliation for symptoms relief is progressively increasing, due to the possibility to significantly prolong survival even in persons affected by metastatic disease. Italian Board of Health, within the National Oncological Plan 2010-2012, gave “simultaneous care” the recognition as the most qualified model to ensure the best result regarding life expectation, quality of life, adherence to therapies. Methods: In Italy’s veneto region health district 8 a unit dedicated to palliative care works in cooperation with oncology clinic, medical wards, general practitioner, social services; periodical meetings are scheduled to review all the requests; each patient is given a multidimensional evaluation, to assess the care needs. The Unit is able to provide a daily home-care, with total parenteral nutrition if needed, management of infusional devices, invasive procedures such as paracentesis, in order to minimize the number of intervening hospital admissions. We considered the percentage of patients who received a simultaneous care approach between 2008 and 2010, the number of patients who died at home or in a hospice, the average time-period of care, the number of elapsing hospital admissions. Results: In 2008 268 new patients received assistance by the Palliative Care Unit, 273 new patients in 2009 and 434 new patients in 2010; 82 (31,3%), 70 (25,6%) and 111 (25,6%) were affected by advanced cancer, respectively; in 2008 208 patients out of 262 (79,4%) died at home or in a hospice, in 2009 224 patients out of 273 (82,1%), in 2010 376 patients out of 434 (86,7%); in 2008 the average time-period of care was 93 days (calculated as the ratio between the total number of days of assistance to patients as a whole and the number of patients), 88 days in 2009; in 2008 the average number of intervening hospital admissions was 0,26 (calculated as the ratio between the number of admissions and the number of patients), 0,28 in 2009. Conclusions: Our data show that the earlier the patient affected by advanced cancer is evaluated by Palliative care Unit, the higher is the likelihood to develop an adequate home- or hospice-base care plan.
Elevated risk of second malignant neoplasms in pediatric germ cell tumor patients.
Authors: Maria Clarissa de Faria Soares Rodrigues, Carlos Rodriguez-Galindo, Karina Braga Ribeiro, A. Lindsay Frazier
Journal: Journal of Clinical Oncology (2013)

10010 Background: The probability of cure is very high for children with germ cell tumors (GCT), but late effects from cisplatinum can be quite significant. In addition to the immediate effects of oto-, neuro and nephrotoxicity, data from men treated for testicular cancer shows that the rate of second malignant neoplasm (SMN) is doubled and that a man treated before age 20 has a 50% chance of SMN by age 75. This study was designed to assess the risk of SMN among individuals treated for malignant GCT during childhood. Methods: We included all patients 0-19 years old with a primary diagnosis of malignant GCT registered in the Surveillance, Epidemiology and End Results (SEER) in the period 1973-2008. We analyzed tumors occurring at least 12 months after the first primary. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated using SEER Stat, version 8.0.1. Results: The cohort comprised 1997 patients (798 women and 1,199 men); 86.3% had primary gonadal tumors (91% in men and 79.5% in women). The median age at diagnosis of the primary malignancy was 17 years (17 for males ; 15 for females), and for second malignancies was 27 (27 for males; 30 for females). Fifty eight SMNs were observed (21 in females; 37 in males). Among women, higher risk was observed to developing breast cancer (n=5; SIR=1.29; 95% CI= 0.42-3.02), thyroid cancer (n=5; SIR= 3.40; 95% CI= 1.1-7.93) and brain cancer (n=3; SIR= 9.19; 95% CI=1.89-26.85). Twenty-seven out of 37 second primary tumors observed in men were contralateral testicular tumors, conferring a 16.2 fold higher risk of developing this neoplasm (95% CI= 10.67-23.58). When the analysis excluded testis as a second site, a higher risk was noted for the development of pancreatic cancer (SIR=19.06; 95% CI=2.31-68.83) and leukemia (SIR=3.55; 95% CI=0.43-12.81). Conclusions: Rates of SMN are elevated in both men and women treated as children for pediatric germ cell tumors. Men need to be made aware of risk in contralateral testicle. The rates of SMN may continue to rise with longer follow up. The attribution of treatment type to risk of SMNs is not possible due to the lack of this information in SEER database.
Prospective randomized phase II trial of oral vinorelbine (NVBo) and cisplatin (P) or pemetrexed (Pem) and P in first-line metastatic or locally advanced non-small cell lung cancer (M or LA NSCLC) patients (pts) with nonsquamous (non SCC) histologic type: NAVoTRIAL01—Preliminary results.
Authors: Jaafar Bennouna, Petr Zatloukal, Maciej Jerzy Krzakowski, Jens Kollmeier, Alain Riviere, Eric Dansin, Monika Serke, Adolfo G. Favaretto, Libor Havel, Stephanie Malasse, Fabienne Biville-Hedouin, Eng Huat Tan
Journal: Journal of Clinical Oncology (2012)

7575 Background: NVBo+P is considered as a standard treatment (trt) in M or LA NSCLC. The recent approval of Pem+P as front line chemotherapy (CT) for non-SCC demonstrates that today, histology could become a “new guidance” to treat patients (pts). Phase III trial (Scagliotti. JCO 2008) showed efficacy of Pem+P in patients with non-SCC pts. Moreover, the higher chemosensitivity of non-SCC is recognised and reported with other chemotherapies (Ardizzoni.JNCI 2007). In GLOB 3 study, NVBo+P also showed better survival in adenocarcinoma (11.7m) than in SCC (8.9m) (Tan.Ann of Oncol 2009). This trial was set up to assess the efficacy of NVBo+P compared to Pem+P for pts with non-SCC histological type. The primary end-point was disease control rate (DCR) including overall response rate (ORR) and stable disease (SD). Methods: Pts were randomised to receive NVBo 80 mg/m² D1D8 (60 at Cycle 1) + P 80 mg/m² D1 q3w or Pem 500 mg/m² + P 75 mg/m² D1 q3w. After 4 cycles of trt, for pts showing a disease control, single agent as continuation maintenance (CM) was proposed until progression or toxicity. Given that Pem+P is now considered as a reference trt in non-SCC, pts were randomised on a 2/1 basis and stratified according to stage (IIIB - IV - relapse), non-SCC confirmed by histology or cytology, gender, smoking status and centre. Results: From 10/09 to 02/11, 153 pts were randomised to receive NVBo+P (102 pts) or Pem+P (51 pts). The efficacy between the 2 arms is similar: The ORR/DCR (Recist 1.1) after 4 cycles of trt are 26%/75% in the NVBo arm (100 eval pts in ITT population) and 24%/78% in the Pem arm (50 eval pts in ITT population). At the end of December 2011, 7 patients are still treated in CM: 5 pts in the NVBo arm and 2 pts in the Pem arm. Conclusions: The 2 CT regimen, NVBo+P or Pem+P have a similar efficacy in terms of ORR/DCR for pts with advanced non-SCC NSCLC. These results appear to be in line with the published data. As the analysis is currently in progress, final results including safety data, PFS and OS will be presented during the meeting.
Allergen immunotherapy with the hypoallergenic B‐cell epitope‐based vaccine BM32 modifies IL‐10‐ and IL‐5‐secreting T cells
Authors: Michèle Myriam Rauber, Christian Möbs, Raffaela Campana, Rainer Henning, Manuel Schulze‐Dasbeck, Brandon Greene, Margarete Focke‐Tejkl, Milena Weber, Rudolf Valenta, Wolfgang Pfützner
Journal: Allergy (2019)

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Abstract 13929: A Facilitated Home Based Rehabilitation Intervention: Impact on Well-Being and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Chim C Lang, Karen Smith, Jenny Wingham, Victoria Eyre, C J Greaves, Fiona Warren, Colin Green, Kate Jolly, Davis Russell, Charles Abhraham, Jackie Austin, Patrick Doherty, Kevin Paul, Sally Singh, Van Lingen Robin L Robin, Sarah Buckingham, Christopher Hayward, Hayes Dalal, Rod Taylor
Journal: Circulation (2017)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is characterised by exercise intolerance and lack of effective pharmacological therapies. However, trials of exercise-based card...
Prognostic value of waterfall plots with the addition of nontarget lesion data.
Authors: William Leonard Mietlowski, Andrew Marc Stein, Weichao Bao, Roger J. Waltzman, Patricia Ann Wood
Journal: Journal of Clinical Oncology (2013)

11082 Background: In patients with solid tumors, the use of a waterfall plot displaying the best percentage change in sum of the longest diameters of target lesions per patient is a common way to depict anti-tumor activity for cytostatic agents (Booth 2008, Dhani 2009). This representation assumes that the best percentage change represents the maximum anti-tumor activity for each patient. Information about new lesions and/or changes in non-target lesions is not incorporated in the waterfall plot; yet these additional events were found to be significant prognostic factors for overall survival adjusting for change in the target lesions (Litiere 2012, Suzuki 2012). Methods: We analyzed two phase III lung cancer trials of 1st and 2nd line combination chemotherapy ± ASA404 (ATTRACT-1,n=1299, ATTRACT-2, n= 920). For patients whose best response in the target lesions was shrinkage, we calculated how often this best response was synchronously accompanied by non-target disease progression. Results: See Table. Conclusions: There can be substantial tumor shrinkage in target lesions synchronously with progressive disease outside the target lesions. Therefore, graphical displays of anti-tumor activity should consider incorporating new and non-target lesion information, as well as target lesion tumor burden. We propose an extended waterfall plot presenting a more complete assessment of anti-tumor activity by incorporating non-target lesion information. We illustrate its utility in an additional data set, the RECORD-1 phase III renal cell cancer trial. Clinical trial information: NCT00662597. [Table: see text]
ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer
Authors: Andrew J. Armstrong, Russell Z. Szmulewitz, Daniel P. Petrylak, Jeffrey Holzbeierlein, Arnauld Villers, Arun Azad, Antonio Alcaraz, Boris Alekseev, Taro Iguchi, Neal D. Shore, Brad Rosbrook, Jennifer Sugg, Benoit Baron, Lucy Chen, Arnulf Stenzl
Journal: Journal of Clinical Oncology (2019)

Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC).ARCHES (ClinicalTrials.gov identifier: NCT02677896) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival.As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT (P < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events.Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer.
Assessment of Inflammation in Pulmonary Artery Hypertension by <sup>68</sup>Ga-Mannosylated Human Serum Albumin
Authors: Jun-Bean Park, Minseok Suh, Ji Yong Park, Jin Kyun Park, Yong-il Kim, Hyunah Kim, Ye Seul Cho, Hyejeong Kang, Kibyung Kim, Jae-Hoon Choi, Jin-Wu Nam, Hyung-Kwan Kim, Yun-Sang Lee, Jae Min Jeong, Yong-Jin Kim, Jin Chul Paeng, Seung-Pyo Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).Methods: We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and 68Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of 68Ga-NOTA-MSA PET was explored in patients with PAH.Measurements and Main Results: Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of 68Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of 68Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of 68Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (P = 0.009) or than those with pulmonary hypertension by left heart disease (P = 0.019) (n = 5 per group).Conclusions:68Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that 68Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.
Pneumonia <i>versus</i> graft dysfunction as the cause of acute respiratory failure after lung transplant: a 4-year multicentre prospective study in 153 adults requiring intensive care admission
Authors: Cristopher Mazo, Teresa Pont, Maria A. Ballesteros, Eloísa López, Luzdivina Rellán, Juan C. Robles, Jordi Rello
Journal: European Respiratory Journal (2019)

We aimed to assess the main causes of intensive care unit (ICU) readmissions in lung transplant adults and to identify independent predictors of ICU mortality (primary end-point). This Spanish five-centre prospective cohort study enrolled all lung transplant adults with ICU readmissions after post-transplant ICU discharge between 2012 and 2016. Patients were followed until hospital discharge or death. 153 lung transplant recipients presented 174 ICU readmissions at a median (interquartile range) of 6 (2–25) months post-transplant. Chronic lung allograft dysfunction was reported in 39 (25.5%) recipients, 13 of whom (all exitus) had restrictive allograft syndrome (RAS). Acute respiratory failure (ARF) (110 (71.9%)) was the main condition requiring ICU readmission. Graft rejection (six (5.4%) acute) caused only 12 (10.8%) readmissions whereas pneumonia (56 (36.6%)) was the main cause (50 admitted for ARF and six for shock), with Pseudomonas aeruginosa (50% multidrug resistant) being the predominant pathogen. 55 (35.9%) and 69 (45.1%) recipients died in the ICU and the hospital, respectively. Bronchiolitis obliterans syndrome (BOS) stage 2 (adjusted OR (aOR) 7.2 (95% CI 1.0–65.7)), BOS stage 3 (aOR 13.7 (95% CI 2.5–95.3)), RAS (aOR &gt;50) and pneumonia at ICU readmission (aOR 2.5 (95% CI 1.0–7.1)) were identified in multivariate analyses as independent predictors of ICU mortality. Only eight (5.2%) patients had positive donor-specific antibodies prior to ICU readmission and this variable did not affect the model. ARF was the main condition requiring ICU readmission in lung transplant recipients and was associated with high mortality. Pneumonia was the main cause of death and was also an independent predictor. RAS should receive palliative care rather than ICU admission.
Reply to Boulet and Nair: Inhaled Corticosteroids and Adult Asthma
Authors: Richard Beasley, James Harper, Grace Bird, Ingrid Maijers, Mark Weatherall, Ian D. Pavord
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

adverse effects.Doses of ICS may be minimized by various measures, including environmental control, use of adjunct therapies such as long-acting inhaled bronchodilators, and in the more severe patient, by the early introduction of biologics.However, prevention of OCS use and related exacerbations should be a priority, which could be avoided in some patients by using high doses of ICS.In this regard, in a study over a median period of 10 years (maximum, 30 yr), we showed that when the dose of ICS/prednisone was adjusted to keep sputum eosinophils under control, exacerbations and the rate of decline of lung function were significantly reduced, although at a price of adverse effects, mainly when OCS was needed (7).Adverse effects of high doses of ICS have been confounded by methodologic issues and intercurrent OCS use, and there is probably also a variation in susceptibility to those effects from one patient to another.We therefore agree with Beasley and colleagues that we should prevent overdosing with ICS when not necessary, and that in this regard, there is a significant care gap in asthma management with an underutilization of noninvasive measurements of airway inflammation, particularly in moderate to severe asthma.We endorse the need for rigorous dose-response studies of ICS to be conducted in patients who are well characterized on the basis of their inflammatory endotypes.
FRI0012 Adverse events, drug withdrawal and efficacy of leflunomide in unselected outpatients with rheumatoid arthritis
Authors: L Mourad, EN van Roon, TL Jansen, PM Houtman, GA Bruyn, EN Griep, WA Baars, JR Brouwers
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Leflunomide (LEF) is a disease modifying antirheumatic prodrug with immunomodulating, antiproliferative and antiinflammatory properties. We studied our first daily practice experience with LEF in the Outpatient Department of Rheumatology. <h3>Methods</h3> In this prospective study we included all consecutive patients with active rheumatoid arthritis (RA), starting treatment with LEF from February 2000 to January 2001. From patient records data were collected, like patient characteristics, medication data and Disease Activity Scores (DAS28). Analysis was performed on intention to treat basis. Primary endpoints are occurrence of adverse events possibly related to LEF use, incidence and reasons for LEF withdrawal and change in DAS28. <h3>Results</h3> 110 patients (n = 38 men and n = 72 women), mean age (SD) 65 (13) years and a median disease duration of 5.5 years were included; mean follow up (SD) was 170 (91) days. Last DMARD prescribed prior to LEF was methotrexate (MTX) 28%, sulfasalazine (SASP) 25%, hydroxychloroquine (HCQ)18% and others 10%; 19% of the patients used LEF as first DMARD. Mean number of DMARDs prescribed before starting LEF was 1.8 ± 1.4. In 9% of the patients LEF was given in combination with another DMARD [MTX (6%), HCQ (2%) or SASP (1%)]. Adverse events (AE) possibly related to LEF use occurred in 56% of patients during follow up, most frequently involving the gastrointestinal tract (62 AE) and skin (21 AE). During follow up 27% discontinued LEF, 16% due to side effects, 5.5% due to inadequate response, 4.5% due to a combination of both. For 1% an undefined cause for withdrawal was recorded. The incidence density for withdrawal of LEF treatment is 56.6 per 100 patient years. Using the change in DAS28 as an efficacy parameter, at the first follow up visit (mean two months) after starting LEF, 22% were categorised good, 48% moderate and 30% non responder. At the second visit (mean six months) 26%, 42% and 31% were categorised good, moderate or non responder. <h3>Conclusion</h3> In an outpatient rheumatology practice the incidence density per patient year for withdrawal of LEF treatment is high. Adverse events were the most frequent reasons for withdrawal; gastro-intestinal tract and skin being the organ (systems) most frequently involved. Using the change in DAS28 as efficacy parameter at the sixth month 68% were categorised as good and moderate responders to LEF.