tbuckley/cabot-search huggingface dataset:
Five-year follow-up of SWOG S0816: limitations and values of a PET-adapted approach with stage III/IV Hodgkin lymphoma
Authors: Deborah M. Stephens, Hongli Li, Heiko Schöder, David J. Straus, Craig H. Moskowitz, Michael LeBlanc, Lisa M. Rimsza, Nancy L. Bartlett, Andrew M. Evens, Ann S. LaCasce, Paul M. Barr, Michael V. Knopp, Eric D. Hsi, John P. Leonard, Brad S. Kahl, Sonali M. Smith, Jonathan W. Friedberg
Journal: Blood (2019)
Impact on the cosmetic outcome of concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conservative surgery: Differences between patient’s and doctor’s views
Authors: A. Toledano, P. Garaud, D. Serin, A. Fourquet, J. Bosset, N. Breteau, G. Body, D. Azria, I. Suzanne, G. Calais
Journal: Journal of Clinical Oncology (2006)

8554 Purpose: A multicenter randomized study comparing after breast-conservative surgery, sequential versus concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEI). After a median follow-up of 6.7 (4.3–9) years, we assessed prospectively late effects and cosmesis satisfaction of these two strategies. Methods and material: After breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (arm A) or CT administered concurrently with the same normofractinnated breast RT (arm B).With structured questions, 214 patients (107 in each arm) rated their satisfaction considering cosmesis, the difference in overall appearance, and specific changes of the breast. Late toxicity (LENT/SOMA scale) and cosmesis were blinded to treatment and assessed by a radiation oncologist by a qualitative scale and another semi-qualitative and semi-quantitative evaluation. Results: Subcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Patient’s cosmesis satisfaction was not statistically different between the two arms with 92.6% of good results in arm A and 86% in arm B (p=0.72); although patients have found more important differences in the treated breast in arm B than in arm A, with 28.8% vs 14.3% of bad results, respectively. Physician’s prospective assessment found less favorable cosmesis results with concomitant treatment than with sequential one, with 40% and 15% of unsatisfaction, respectively (p=0.0014) using a semi-quantitative and qualitative scale; The use of a subjective 5-point scale found also a worse physician’s cosmesis satisfaction in arm B than in arm A (p=0.0013) Conclusion: The concurrent use of CT with RT is significantly associated with an increase incidence of grade 2 or greater late side effects. Rating of cosmesis is also subjective. Patients’ satisfaction with cosmesis is greater than the doctors’ for concomitant radiochemotherapy in breast cancer, and is not only determined by radiation late effects. With two methods, physician found a worse cosmesis outcome for concomitant radiochemotherapeutic arm. No significant financial relationships to disclose.
Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline
Authors: Noam Yarom, Charles L. Shapiro, Douglas E. Peterson, Catherine H. Van Poznak, Kari Bohlke, Salvatore L. Ruggiero, Cesar A. Migliorati, Aliya Khan, Archie Morrison, Holly Anderson, Barbara A. Murphy, Devena Alston-Johnson, Rui Amaral Mendes, Beth Michelle Beadle, Siri Beier Jensen, Deborah P. Saunders
Journal: Journal of Clinical Oncology (2019)

To provide guidance regarding best practices in the prevention and management of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer.Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. Guideline development involved a systematic review of the literature and a formal consensus process. PubMed and EMBASE were searched for studies of the prevention and management of MRONJ related to bone-modifying agents (BMAs) for oncologic indications published between January 2009 and December 2017. Results from an earlier systematic review (2003 to 2008) were also included.The systematic review identified 132 publications, only 10 of which were randomized controlled trials. Recommendations underwent two rounds of consensus voting.Currently, MRONJ is defined by (1) current or previous treatment with a BMA or angiogenic inhibitor, (2) exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region and that has persisted for longer than 8 weeks, and (3) no history of radiation therapy to the jaws or metastatic disease to the jaws. In patients who initiate a BMA, preventive care includes comprehensive dental assessments, discussion of modifiable risk factors, and avoidance of elective dentoalveolar surgery (ie, surgery that involves the teeth or contiguous alveolar bone) during BMA treatment. It remains uncertain whether BMAs should be discontinued before dentoalveolar surgery. Staging of MRONJ should be performed by a clinician with experience in the management of MRONJ. Conservative measures comprise the initial approach to MRONJ treatment. Ongoing collaboration among the dentist, dental specialist, and oncologist is essential to optimal patient care.
Not All Home-based Exercise Programs Are Home-based Pulmonary Rehabilitation Programs
Authors: Marilyn L. Moy
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

To further put these changes into clinical context, we previously measured IOS in response to propranolol-induced bronchoconstriction in patients with asthma where there was a 0.05 (kPa/L) $ s increase in R5 2 R20 corresponding to a 104.1% (95% CI, 22.6 to 185.6%) change, along with a subsequent bronchodilator response to salbutamol of 20.17 (kPa/L) $ s and 2115.6%(95% CI, 255.6% to 2175.7%), respectively (2).Moreover, in a health informatics evaluation of 302 patients with asthma, there was a 45% increased risk for worse control in relation to oral corticosteroid use, and 47% in relation to inhaled albuterol use measured during a 2-year period when comparing cohorts of patients with asthma, using a cutoff value for R5 2 R20 of less than or greater than 0.07 (kPa/L) $ s (3).Hence, the small airway asthma phenotype reflected by abnormal R5 2 R20 is associated with poorer control.We believe the findings of Foy and colleagues (1) are important in further validating the use of IOS in determining effects of treatments on small airways of patients with asthma.
Abstract 1630: Uric Acid Revisited: Interrelationships with Low-Grade Inflammation, Adiponectin and Arterial Stiffness in Essential Hypertension
Authors: Costas Tsioufis, Kyriakos Dimitriadis, Dimitris Chatzis, Dimitris Tsiachris, Karmen Vasiliadou, Dimitris Tousoulis, Christodoulos Stefanadis, Ioannis Kallikazaros
Journal: Circulation (2007)

Introduction: Increased uric acid (UA) levels are associated with high cardiovascular risk, while subclinical inflammation, arterial stiffening and hypoadiponectinemia contribute to atherosclerosis progression. Hypothesis: Serum UA levels may be related to high-sensitivity C-reactive protein (hs-CRP), adiponectin and arterial stiffness in essential hypertensives. Methods: In our population of 292 newly diagnosed untreated non-diabetic patients with stage I to II essential hypertension [190 men, aged 50 years, office blood pressure (BP)=148/95 mmHg], the distribution of UA was split by the median (5.3 mg/dl) and accordingly subjects were classified into those with high and low values. In all participants, arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV), by means of a computerized method (Complior SP). Results: Patients with high UA (n=143) compared to those with low UA (n=149) exhibited higher 24-h systolic BP (139±12 vs 132±11 mmHg, p&lt;0.0001), while did not differ regarding age, body mass index and lipid profile (p=NS). Those with high UA compared to those with low UA had increased levels of hs-CRP (3.1±1.4 vs 2.3±1.2 mg/l, p&lt;0.05) and PWV (8.7±1.2 vs 7.9±1.2 m/sec, p&lt;0.05), whereas exhibited lower adiponectin (8.1±2.4 vs 9.7±2.8 μg/ml, p&lt;0.05). In the entire population, UA was positively associated with 24-h systolic BP (r=0.297, p&lt;0.0001), hs-CRP (r=0.204, p&lt;0.001) and PWV (r=0.165, p=0.009), while it was negatively related to adiponectin (r=−0.218, p&lt;0.0001). In multiple regression analysis, 24-h systolic BP (b=0.246, p&lt;0.001), hs-CRP (b=0.142, p&lt;0.05) and adiponectin (b=−0.154, p≥0.05) were independent predictors of UA. Analysis of covariance revealed that hs-CRP, PWV and adiponectin values were significantly different between groups after adjustment for confounders (p&lt;0.05). Conclusions: Increased UA levels in essential hypertension are paralleled by a state of pronounced inflammatory activation, hypoadiponectinemia and accelerated arterial stiffening. These findings suggest that UA is interrelated with diverse mediators of vascular dysfunction, underscoring its pluripotent nature in the progression of the hypertensive atherosclerotic disease.
Detrimental effects of air pollution on adult lung function
Authors: Edith B. Milanzi, Ulrike Gehring
Journal: European Respiratory Journal (2019)

Air pollution, including ambient and household air pollution, is considered one of the world's largest environmental health threats and was estimated to account for 4.9 million deaths and 147 million years of healthy life lost around the world in 2017 [1]. Compelling evidence for adverse effects of air pollution on a vast array of health outcomes, in particular cardiovascular and respiratory health, has been established [2, 3]. Air pollution exposure may lead to lower lung function and higher risk of chronic obstructive pulmonary disease in adults <http://bit.ly/2IpGx9j>
A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1–3 inhibitor, cediranib, in recurrent women’s cancers with biomarker analyses
Authors: Alexandra S. Zimmer, Erin Nichols, Ashley Cimino-Mathews, Cody Peer, Liang Cao, Min-Jung Lee, Elise C. Kohn, Christina M. Annunziata, Stanley Lipkowitz, Jane B. Trepel, Rajni Sharma, Lekha Mikkilineni, Margaret Gatti-Mays, William D. Figg, Nicole D. Houston, Jung-Min Lee
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Strategies to improve activity of immune checkpoint inhibitors are needed. We hypothesized enhanced DNA damage by olaparib, a PARP inhibitor, and reduced VEGF signaling by cediranib, a VEGFR1–3 inhibitor, would complement anti-tumor activity of durvalumab, a PD-L1 inhibitor, and the 3-drug combination would be tolerable. <h3>Methods</h3> This phase 1 study tested the 3-drug combination in a 3 + 3 dose escalation. Cediranib was taken intermittently (5 days on/2 days off) at 15 or 20 mg (dose levels 1 and 2, respectively) with durvalumab 1500 mg IV every 4 weeks, and olaparib tablets 300 mg twice daily. The primary end point was the recommended phase 2 dose (RP2D). Response rate, pharmacokinetic (PK), and correlative analyses were secondary endpoints. <h3>Results</h3> Nine patients (7 ovarian/1 endometrial/1 triple negative breast cancers, median 3 prior therapies [2–6]) were treated. Grade 3/4 adverse events include hypertension (1/9), anemia (1/9) and lymphopenia (3/9). No patients experienced dose limiting toxicities. The RP2D is cediranib, 20 mg (5 days on/2 days off) with full doses of durvalumab and olaparib. Four patients had partial responses (44%) and 3 had stable disease lasting ≥6 months, yielding a 67% clinical benefit rate. No significant effects on olaparib or cediranib PK parameters from the presence of durvalumab, or the co-administration of cediranib or olaparib were identified. Tumoral PD-L1 expression correlated with clinical benefit but cytokines and peripheral immune subsets did not. <h3>Conclusions</h3> The RP2D is tolerable and has preliminary activity in recurrent women's cancers. A phase 2 expansion study is now enrolling for recurrent ovarian cancer patients. <h3>Trial registration</h3> ClinicalTrials.gov identifier: NCT02484404. Registered June 29, 2015.
Targeting Cancer Cell Metastasis by Converting Cancer Cells into Fat
Authors: Dana Ishay-Ronen, Gerhard Christofori
Journal: Cancer Research (2019)

Cancer is a systemic heterogeneous disease that can undergo several rounds of latency and activation. Malignant tumors evolve through dynamic responses to microenvironmental signals and development of resistance following therapeutic interventions. Cancer cell adaptation is required for cell survival during metastatic dissemination and outgrowth. Epithelial-mesenchymal transition (EMT) plays a major role in facilitating cell plasticity in cancer and allows cancer cells to escape chemotherapies and targeted therapies through dedifferentiation and signaling adaptation processes. In our recent study, we showed that breast cancer cells that have undergone EMT can be terminally differentiated into adipocytes using the PPARγ agonist rosiglitazone combined with the MEK inhibitor trametinib. The conversion of invasive cancer cells into adipocytes repressed primary tumor invasion and metastasis formation in mouse models of breast cancer. The transdifferentiated cancer cell-derived adipocytes were growth-arrested and lost their cellular plasticity. These results indicate the high potential of utilizing the increased cell plasticity inherent to invasive cancer cells for transdifferentiation therapy.
HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway
Authors: Dao-Jun Lv, Xian-Lu Song, Bin Huang, Yu-Zhong Yu, Fang-Peng Shu, Chong Wang, Hong Chen, Hai-Bo Zhang, Shan-Chao Zhao
Journal: Theranostics (2019)

Background and Aim: We have previously shown that high-mobility group box 1 (HMGB1) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of HMGB1 in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of HMGB1 in PCa tumorigenesis. Methods: Gain-of-function and loss-of-function experiments were used to determine the biological functions of HMGB1 both in vitro and in vivo. Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between HMGB1 and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of HMGB1 and its relationship with Brahma-related gene 1 (BRG1) was examined by immunohistochemistry. Results: The results demonstrated that ectopic expression of HMGB1 facilitated growth and metastasis of PCa by enhancing Akt signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of HMGB1 showed the opposite effects. Mechanistically, HMGB1 exerted these functions through its interaction with BRG1 which may augment BRG1 function and activate the Akt signaling pathway thereby promoting EMT. Importantly, both HMGB1 and BRG1 expression was markedly increased in human PCa tissues. Conclusions: Taken together, these findings indicate that upregulation of HMGB1 promotes PCa development via activation of Akt and accelerates metastasis through regulating BRG1-mediated EMT. HMGB1 could be used as a novel potential target for the treatment of PCa.
First-in-human study of AMG 655, a pro-apoptotic TRAIL receptor-2 agonist, in adult patients with advanced solid tumors
Authors: P. LoRusso, D. Hong, E. Heath, R. Kurzrock, D. Wang, M. Hsu, L. Goyal, J. Wiezorek, C. Storgard, R. Herbst
Journal: Journal of Clinical Oncology (2007)

3534 Introduction: AMG 655 is a fully human monoclonal agonist antibody that binds human TRAIL receptor 2 (TR-2/DR5), activates caspases, and induces apoptosis in sensitive tumor cells. The primary objectives of this ongoing first-in-human study were to assess the safety, tolerability, and pharmacokinetics (PK) of AMG 655 in patients (pts) with advanced solid tumors. Methods: Three to 9 pts were enrolled into 1 of 5 sequential dose cohorts (0.3, 1, 3, 10, or 20 mg/kg) of AMG 655 administered intravenously Q2W. No AMG 655 was administered on day 43 to allow assessment of terminal PK parameters. RECIST and FDG-PET were analyzed by central radiology. Pts remained on study until tumor progression or unacceptable toxicities occurred. Results: As of October 19, 2006, 16 pts (4 in the 10 mg/kg cohort; 3 in each of the other cohorts) had received = 1 dose of AMG 655; 12 pts were men, mean (SD) age was 53 (±8.9) years. No DLTs or AMG 655-related serious AEs were reported. The MTD was not reached. Nine pts reported AMG 655-related AEs. Treatment-related AEs in 3 or more pts were: pyrexia (4 pts), fatigue (3 pts), and hypomagnesaemia (3 pts). Fatigue and elevated serum lipase were the only grade 3 or higher AMG 655-related AEs and both occurred in the same pt (0.3-mg/kg cohort). No anti-AMG 655 antibodies were detected. PK data were available from dose cohorts 1 to 3 (0.3, 1, and 3 mg/kg); AMG 655 demonstrated dose-linear kinetics with a half-life of ∼10 days. Tumor- response data were available for 13 pts. Partial response was observed in 1 pt with non-small cell lung cancer (NSCLC) who experienced a 46% reduction in tumor volume by RECIST and remains on study after 48 weeks. Stable disease was reported in 4 pts (range 6 to 35 weeks), and progressive disease in 8 pts. One pt with colorectal cancer and stable disease demonstrated a metabolic partial response with a 34% reduction in maximum standardized uptake value (SUV max ). Conclusions: AMG 655 administered up to 20 mg/kg Q2W appeared to be well tolerated in these pts. The anti-tumor activity of AMG 655 was confirmed with observation of a partial response in NSCLC and a metabolic partial response in colorectal cancer. Further studies evaluating AMG 655 in combination with chemotherapy and targeted agents are warranted. No significant financial relationships to disclose.
The effect of HCV serological status on doxorubicin-based chemotherapy-induced toxicity and disease-free survival in breast cancer patients.
Authors: Salah-Eldin Abd-El-Moneim, Karim Youssry Welaya, Shaaban El-Assal, Ossama Eissa Salama, Hamdy M. Ghanem
Journal: Journal of Clinical Oncology (2013)

1075 Background: Breast cancer and HCV are two frequent diseases in Egypt. There is a considerable probability of concurrent affection. This concurrence creates a subpopulation which needs special evaluation and care. Methods: To evaluate a subset of Egyptian breast cancer patients receiving doxorubicin based adjuvant chemotherapy, with HCV seropositivity (Group 2) compared to HCV seronegative patients (Group 1). 102 breast cancer patients, planned to receive Doxorubicin based adjuvant chemotherapy, at the Oncology Department, Alexandria Faculty of Medicine, were recruited since June 2009. Pretreatment evaluation included serological testing for HCV. FAC adjuvant chemotherapy was given. Results: HCV seropositivity was detected in 52 cases. Two cases in Group 2 developed toxic hepatitis and discontinued treatment and follow up. The remaining 100 patients suffered comparable toxicities, except for more frequent SGOT and SGPT elevations in Group 2. Diarrhea was more frequent in Group 2. Treatment delays and dose reductions were more frequently observed in Group 2. The 24 month disease-free survival and relapse pattern were not significantly different between the two groups. Conclusions: Patients receiving chemotherapy should undergo screening for the virus. Most patients with HCV were able to tolerate chemotherapy and continue the initial chemotherapy plan, without significant change in the toxicity profile or the natural course of their malignancy. Dose or regimen adjustments may be of help to less tolerant patients. A preemptive 10% initial Doxorubicin dose reduction might reduce the frequency of severe toxicity. The assistance of a gastroenterologist in HCV positive breast cancer patients, planned for chemotherapy is important.
Abstract 256: Therapeutic Hypothermia Decreases Arrhythmia Substrates by Attenuating Repolarization Current IK,ATP During Myocardial Ischemia
Authors: Joseph S Piktel, David S Rosenbaum, Lance D Wilson
Journal: Circulation (2011)

Background: While hypothermia is arrhythmogenic, the effect of therapeutic hypothermia (TH) performed after cardiac arrest on susceptibility to arrhythmias is not well understood. Clinically, patie...
Multiplex quantitative analysis of cancer-associated fibroblasts and immunotherapy outcome in metastatic melanoma
Authors: Pok Fai Wong, Wei Wei, Swati Gupta, James W. Smithy, Daniel Zelterman, Harriet M. Kluger, David L. Rimm
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> The cancer-associated fibroblast (CAF) population is implicated in immune dysregulation. Here, we test the hypothesis that CAF profiles in pretreatment tumor specimens are associated with response to immune checkpoint blockade of programmed cell death 1 (PD-1). <h3>Methods</h3> Pretreatment whole tissue sections from 117 melanoma patients treated with anti-PD-1 therapy were assessed by multiplex immunofluorescence to detect CAFs defined by Thy1, smooth muscle actin (SMA), and fibroblast activation protein (FAP). Two independent image analysis technologies were used: inForm software (PerkinElmer) to quantify cell counts, and AQUA™ to measure protein by quantitative immunofluorescence (QIF). CAF parameters by both methodologies were assessed for association with previously measured immune markers (CD3, CD4, CD8, CD20, CD68, PD-L1), best overall response, progression-free survival (PFS), and overall survival (OS). <h3>Results</h3> CAF parameters, by cell counts or QIF, did not correlate with immune markers nor with best overall response. However, both Thy1 and FAP cell counts had significant positive associations with PFS (all <i>P</i> &lt; 0.05) and OS (all <i>P</i> &lt; 0.003). SMA cell counts showed negative associations with outcome in anti-PD-1 treated patients. Similar associations were not observed in a control cohort of historical melanoma patients predating immunotherapy. Instead, FAP was a negative prognostic biomarker (<i>P</i> = 0.01) in the absence of immunotherapy. Multivariable analyses revealed significant PFS and OS associations with the CAF parameters were independent of baseline variables. <h3>Conclusions</h3> Pretreatment CAF profiles are associated with melanoma immunotherapy outcome. Multiplex CAF analysis has potential as an objective companion diagnostic in immuno-oncology.