tbuckley/cabot-search huggingface dataset:
Remission in SLE: the duration depends on multiple factors, including the definition
Authors: Andrea Doria, Margherita Zen, Luca Iaccarino
Journal: Annals of the Rheumatic Diseases (2016)

Remission in SLE: the duration depends on multiple factors, including the definition We read with great interest the article from Wilhelm et al 1 published on Annals of the Rheumatic Diseases.We agree with the authors that remission is an emerging concept in systemic lupus erythematosus (SLE) and that it is very important to find out a definition of remission heralding the best outcome for clinical practice and clinical trials.Although this study, carried out in a very large monocentric cohort of lupus patients, is an important contribution to this topic, its result is a little bit disappointing: indeed, only a minority of lupus patients could maintain a durable remission, which means that, according to this study, remission is not a suitable target for SLE treatment.The percentage of patients with durable remission was so low that the authors did not analyse the effect of remission on disease outcomes such as damage accrual.In our recent paper, 2 we obtained very different results and our patients with durable remission achieved a better outcome compared with unremitted ones.Thus, before considering remission in SLE as a mistaken target, we should critically examine all our results.Apart from the differences in ethnicity, clinical and serological features between the two cohorts, in Wilhelm's study the authors considered all patients who did not satisfy their definitions of remission at baseline and evaluated the time to the first remission and, thereafter, the time to the first flare.Thus, they evaluated only the first remission period per patient and not the longest period of remission over the follow-up, as we did in our study.][5][6][7][8] However, the most important difference between the two studies lies in the definitions of remission and, particularly, the absence of physician global assessment (PGA) in the definitions we used.In Wilhelm's definitions of remission, patients must have both clinical Systemic Lupus Disease Activity Index (cSLEDAI) equal to 0 and PGA score <0.5 in order to be considered as remitted.Remarkably, approximately 40% of patients who did not satisfy the Wilhelm's definitions of remission at study entry had a cSLEDAI score equal to 0 and about 20% had a PGA score <0.5.Thus, the definitions of remission they used were more stringent than our definitions and a discrepancy between cSLEDAI and PGA score could have prevented the fulfilment of the definition of remission in their study.Wilhelm's study is really very useful since it opens the discussion on a very important question: is it better a stringent definition of remission, only achieved by few patients, or a more liberal one associated with a decrease in damage progression?Thus, before considering disease remission a dead target in SLE treatment, we suggest caution in interpreting and reporting the results of the studies on remission in SLE.
Effect of cholesterol and triglyceride increases on time to progression in renal clear cell cancer patients treated with everolimus.
Authors: Francesco Pantano, Giuseppe Procopio, Marianna Silletta, Cinzia Ortega, Francesco Maria Guida, Olga Venditti, Veronica Prati, Marco Imperatori, Chiara Spoto, Elena Verzoni, Salvatore Intagliata, Bruno Vincenzi, Giuseppe Tonini, Mimma Rizzo, Daniele Santini
Journal: Journal of Clinical Oncology (2013)

e15528 Background: An increased level of cholesterolemia (C) and triglyceridemia (T) secondary to an impairment of lipidic metabolism is a well known side effect of all mTOR inhibitors including everolimus. In the phase III pivotal study of everolimus in mRCC patients, an increase of C and T was reported in 77 and 73 % of patients, respectively. Increase of C and T may represent a surrogate parameter related to mTOR pathway inhibition. On these basis, we assessed the value of C and T increase as a factor predicting the efficacy of everolimus in metastatic clear cell renal cancer. Methods: We retrospectively evaluated 46 patients ( 36 male: 10 female; mean age 61.4 years +/- 11.5) with metastatic clear cell renal cancer who received a second/third line with everolimus after at least one tyrosine-kinase inhibitor (TKI). From routinely performed blood test, we retrieved the value of total C and T the day before the first everolimus admnistration and during the entire duration of treatment. We also considered for each patient variations of glycemia, blood pressure and BMI before and after beginning of treatment, as parameters of metabolic syndrome. Time to progression (TTP) and survival were evaluated. Results: Among all the potential predictive factors considered, only the increase of cholesterol and triglyceride (&gt; 20% compared to the baseline) within 2 months from the start of everolimus correlated with efficacy. Median TTP of the 19 patients with total early C upraising was statistically significant higher than in 27 patients without upraising (14.1 months vs 5.5 months, P= 0.009). Conversely, only a positive trend favoring patients with C upraising was recorded in median survival (24.9 months vs 16.0 months, P= 0.163 ). Both median TTP and median survival were found to be statistically significant higher in the 25 patients experiencing T upraising than in the 21 patients who did not (respectively, 13.0 months vs 4.9 months, P= 0.007 and 26.4 months vs 13.4 months, P= 0.018). Conclusions: Early C and T modifications predict everolimus efficacy in renal clear cell cancer.
Case 46-1977
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, William E. Strole, James J. Galdabini
Journal: New England Journal of Medicine (1977)

Presentation of CaseA 68-year-old man was admitted to the hospital because of possible sepsis.There was a long history of hypertension and hypercholesterolemia, for which he received methyldopa and dipyridamole. He was otherwise well until two months before admission, when his right lower leg was crushed in a motor-vehicle accident. He was taken to another hospital, where a fasciotomy was performed because of suspected anterior-tibial-compartment syndrome; numerous blood clots were removed. Wet dressings were begun, and he was discharged home on the seventh hospital day. On follow-up examination several days later necrosis of the skin and superficial infection were . . .
The intersection of radiotherapy and immunotherapy: Mechanisms and clinical implications
Authors: Michael Spiotto, Yang-Xin Fu, Ralph R. Weichselbaum
Journal: Science Immunology (2016)

By inducing DNA damage, radiotherapy both reduces tumor burden and enhances anti-tumor immunity. Here, we will review the mechanisms by which radiation induces anti-tumor immune responses that can be augmented using immunotherapies to facilitate tumor regression. Radiotherapy increases inflammation in tumors by activating the NF-κB and the Type I interferon response pathways to induce expression of pro-inflammatory cytokines. This inflammation coupled with antigen release from irradiated cells facilitates dendritic cell maturation and cross-presentation of tumor antigens to prime tumor-specific T cell responses. Radiation also sensitizes tumors to these T cell responses by enhancing T cell infiltration into tumors and the recognition of both malignant cancer cells and non-malignant stroma that present cognate antigen. Yet, these anti-tumor immune responses may be blunted by several mechanisms including regulatory T cells and checkpoint molecules that promote T cell tolerance and exhaustion. Consequently, the combination of immunotherapy using vaccines and/or checkpoint inhibitors with radiation is demonstrating early clinical potential. Overall, this review will provide a global view for how radiation and the immune system converge to target cancers and the early attempts to exploit this synergy in clinical practice.
Immunobiology of Long Noncoding RNAs
Authors: Maninjay K. Atianand, Daniel R. Caffrey, Katherine A. Fitzgerald
Journal: Annual Review of Immunology (2017)

The discovery of long noncoding RNAs (lncRNA) has provided a new perspective on gene regulation in diverse biological contexts. lncRNAs are remarkably versatile molecules that interact with RNA, DNA, or proteins to promote or restrain the expression of protein-coding genes. Activation of immune cells is associated with dynamic changes in expression of genes, the products of which combat infectious microorganisms, initiate repair, and resolve inflammatory responses in cells and tissues. Recent evidence indicates that lncRNAs play important roles in directing the development of diverse immune cells and controlling the dynamic transcriptional programs that are a hallmark of immune cell activation. The importance of these molecules is underscored by their newly recognized roles in inflammatory diseases. In this review, we discuss the contribution of lncRNAs in the development and activation of immune cells and their roles in immune-related diseases. We also discuss challenges faced in identifying biological functions for this large and complex class of genes.
Rapid intraoperative digital specimen tomosynthesis.
Authors: Cary Steven Kaufman, Valerie Behrndt, Laurie Hill, Rebecca Caro, Sid Nix, Karen Zacharias, Erik Evans, Carol Mahon, Karen Ness, Nancy Schnell
Journal: Journal of Clinical Oncology (2015)

59 Background: About 75% of newly diagnosed breast cancers are not palpable and require image localization to remove the target lesion. Digital specimen mammography devices were developed to identify lumpectomy targets in the operating room. Despite the availability of two-dimensional digital specimen mammography (2D), the re-excision rate for lumpectomy remains significant. Specimen tomosynthesis (3D) may provide a more detailed image than standard 2D with consecutive image slices of the lumpectomy specimens for immediate review. Methods: A consecutive series of 28 breast cancer patients underwent intraoperative specimen imaging with both 2D and 3D imaging. Data recorded for each specimen on each device included 1) accuracy of identification of target lesion, 2) time required to produce comparable images, 3) ease of forwarding images via PACS to radiology, 4) predicted closest margin according to each specimen imaging device compared with final pathologic measured margin, and 5) ease of use by the surgeon and/or nurse. Results: The central focus of all 28 lesions were accurately identified with both 2D and 3D. After a short learning curve, details on the tomosynthesis images were seen not clearly shown on the 2D unit including some spiculated masses and architectural distortions. The location of closest margin was more specific with the 3D device due to “Z-axis” measurements which obtain the vertical distance of the target within the specimen. The spatial relationship of marginal calcifications or marking clips at the edge of the specimen provided by the 3D “Z-axis” was superior to the 2D orthogonal views. Although the time taken to obtain the 3D image was 74 seconds longer than a single image with the 2D device (106 vs. 32 seconds), this was equal to the time taken to obtain the two orthogonal images using the 2D device. Ease of use was equal for both 2D and 3D. Too few patients with positive margins were found to assess a difference in intraoperative positive margin prediction. Conclusions: Our initial experience with 3D tomosynthesis of lumpectomy specimens demonstrate clear images and increased information available for the breast surgeon. Research is planned to further examine the added value of high resolution tomosynthesis in breast surgery.
Pathways through which asthma risk factors contribute to asthma severity in inner-city children
Authors: Andrew H. Liu, Denise C. Babineau, Rebecca Z. Krouse, Edward M. Zoratti, Jacqueline A. Pongracic, George T. O'Connor, Robert A. Wood, Gurjit K. Khurana Hershey, Carolyn M. Kercsmar, Rebecca S. Gruchalla, Meyer Kattan, Stephen J. Teach, Melanie Makhija, Dinesh Pillai, Carin I. Lamm, James E. Gern, Steven M. Sigelman, Peter J. Gergen, Alkis Togias, Cynthia M. Visness, William W. Busse
Journal: Journal of Allergy and Clinical Immunology (2016)
Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non–Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial
Authors: Stephen G. Chun, Chen Hu, Hak Choy, Ritsuko U. Komaki, Robert D. Timmerman, Steven E. Schild, Jeffrey A. Bogart, Michael C. Dobelbower, Walter Bosch, James M. Galvin, Vivek S. Kavadi, Samir Narayan, Puneeth Iyengar, Clifford G. Robinson, Raymond B. Wynn, Adam Raben, Mark E. Augspurger, Robert M. MacRae, Rebecca Paulus, Jeffrey D. Bradley
Journal: Journal of Clinical Oncology (2016)

Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non-small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. Comparisons included 2-year overall survival (OS), progression-free survival, local failure, distant metastasis, and selected Common Terminology Criteria for Adverse Events (version 3) ≥ grade 3 toxicities. Results The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P = .005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distant metastasis-free survival were not different between IMRT and 3D-CRT. IMRT was associated with less ≥ grade 3 pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT for locally advanced NSCLC.
Preliminary safety results of dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (P) with trastuzumab (T) and lapatinib (L) in HER2 overexpressed/amplified breast cancer (BCA)
Authors: C. T. Dang, N. U. Lin, D. Lake, M. N. Dickler, S. Modi, A. D. Seidman, R. M. Steingart, L. Norton, E. P. Winer, C. A. Hudis
Journal: Journal of Clinical Oncology (2008)

518 Background: We showed that dd q 2 weekly (w) AC → P + T×1 year (y) as adjuvant treatment (Rx) for patients (pts) with HER2 (+) BCA is safe with a congestive heart failure (CHF) rate of 1/70 pts (in press, JCO 2008). Lapatinib (L) is effective in HER2/neu (+) pts w/ Stage IV BCA and is being tested in randomized adjuvant trials. We are conducting a pilot study of dd AC → w P + T + L to determine the cardiac safety and feasibility of this combination. The 1° endpoint is cardiac safety defined as discontinuation of T + L due to 1) cardiac death or 2) CHF. The 2° endpoints are to evaluate toxicities, time to recurrence, overall survival, and to explore the use of serial troponin I and C-reactive protein as predictors of cardiac toxicity. Methods: Pts must have HER2 IHC 3+ or FISH-amplified BCA, LVEF > 50% and no active cardiac disease. Rx consists of AC at 60/600 mg/m2×4 q 2 w (w/ pegfilgrastim 6 mg on day 2) → P at 80 mg/m2×12 q w + T×1 y (H 4 mg/kg load and 2 mg/kg q w during P and 6 mg/kg q 3 w after all chemotherapy is completed); L (1,000 mg daily is begun w/ P +T and continued for 1 y). MUGA is obtained at baseline and at months (mo) 2, 6, 9, and 18. Pts with significant asymptomatic LVEF decline after dd AC based on mo 2 MUGA do not receive T + L; pts with significant asymptomatic LVEF decline during T + L may have T + L held permanently. Results: From March 2007 to January 2008, we enrolled 63 of 100 planned pts. Median (med) age is 45 years (range, 28–73). Med baseline LVEF is 68 % (range, 52–79 %). As of January 5, 2008, 44 pts have had mo 2 MUGA after dd AC w/ a med LVEF of 70% (52–81%) and there have been no significant LVEF declines. 10/63 pts are off study (5 G 3 diarrhea, 1 G 2 diarrhea, 1 G 2 rash, 1 POD, 1 death after AC # 2 from adenovirus, 1 G 2 fatigue after AC # 4). Conclusions: This is the first report demonstrating cardiac safety and feasibility of dd AC → w P + T + L. These are the first safety results for the combination arm in the ALLTO trial. Updated results will be available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech, GlaxoSmithKline Bristol-Myers Squibb, Genentech, GlaxoSmithKline Genentech, GlaxoSmithKline
Stereotactic body radiotherapy (SBRT) reirradiation for recurrent pancreas cancer.
Authors: Rabia N Dagoglu, Mark Callery, James Moser, Jennifer F. Tseng, Tara Kent, Andrea J. Bullock, Rebecca A. Miksad, Joseph Douglas Mancias, Anand Mahadevan
Journal: Journal of Clinical Oncology (2015)

451 Background: After adjuvant or definitive radiation for pancreas cancer, there are limited conventional treatment options for recurrent pancreas cancer. We explored the role of (Stereotactic Body Radiotherapy) SBRT for reirradiation of recurrent pancreas cancer. Methods: Our institutional IRB approved database was retrospectively reviewed. All patients were deemed unresectable and treated with systemic therapy. Fiducial gold markers were used. CT simulation was performed with oral and IV contrast and patients were treated with respiratory motion tracking.The choice of fractionation was based on tumor volume, location of the tumor and prior radiation dose, interval between prior RT, adjacent normal tissue, patients’ performance status and co morbidities. The irradiation dose was prescribed to the isodose line covering at least 95% of the target volume. Maximum point dose to the gastric and duodenal walls was kept at or below prescription dose. Results: This study included 30 patients reirradiated for recurrent pancreas cancer at our center between September 2005 and September 2013. 17 males and 13 females were treated. The median age at the time of reirradiation was 67 years (range 44 to 88 years). Median follow-up was 11 months (4 to 24 months).The median target volume was 41.29cc. The median prescription dose was 25Gy (24-36 Gy) in a median of 5 fractions prescribed to a mean 78% isodose line. The median overall survival was 14 months. The 1 and 2 year local control was 78%. The worst toxicity included 3/30(10%) grade III acute toxicity for pain, bleeding and vomiting. There was 2/30 (7%) Grade III long-term bowel obstructions. Conclusions: Management of locally recurrent pancreatic cancer, particularly after prior radiation therapy, is challenging. We report the utility of SBRT for reirradiation of locally recurrent pancreas cancer after prior radiation, with reasonable local control, modest survival and acceptable toxicity. Future prospective studies are needed to define the role of SBRT reirradiation for local recurrences in the setting of systemic therapy.
Evaluating the utility of the QUAL-EC in the clinical care of patients with advanced cancer.
Authors: Anne Wilkinson, Susan Slatyer, Anna Nowak, Cathy Pienaar, Anil Tandon, Mark Wallace
Journal: Journal of Clinical Oncology (2015)

86 Background: We piloted the Quality of Life at the End of Life (QUAL-E) in Australian palliative care in-patients (N=52) and demonstrated feasibility, acceptability and face validity. An unexpected finding was the potential for the QUAL-E to prompt psycho-social-spiritual discussion when conducted as an interview, indicating opportunities for enhanced support. For this study, we compared a 17-item QUAL-E-Cancer (QUAL-EC) to the Distress Thermometer Screening Tool (DT) and participants’ experience when the QUAL-EC was conducted as an interview. Methods: A cross-sectional, mixed methods design was used. Convenience sampling recruited patients (N=50) with advanced cancer and a prognosis of less than 12 months from a tertiary hospital. Participants completed the DT, followed by the QUAL-EC which was digitally recorded as an interview. Results: Correlational and thematic analysis found that 39.6% of participants reported severe distress (score ≥7) while 40% reported moderate distress (score 4-6) on the DT. Levels of distress significantly correlated with two QUAL-EC domains: symptom control (r=0.52, p&lt;0.001) and preparation for end of life (r=0.32, p&lt;0.05). Qualitative analysis identified six themes: the health care team; family issues; approaching death; worry; coping and QUAL-EC experience. Feasibility: completion of the QUAL-EC ranged from 3-14 minutes (M=7.37 minutes, SD 3.05 minutes). Acceptability: Participants overwhelmingly found the questions to be clear and did not find the questions hard to understand, hard to answer or stressful. Ninety percent of participants agreed or strongly agreed that they were glad they took part. Conclusion. Patient distress was associated with either symptom burden or concerns about their family/loved ones. Conclusions: When distress is identified on screening, the QUAL-EC offers good potential for nuanced, versus vague assessment of globalised distress (e.g., DT) as an aid in targeting patient-centered clinical/psycho-social interventions.
Phase I Study of the Combination of Azacitidine (AZA) with MEC (Mitoxantrone, Etoposide and Cytarabine) Salvage Chemotherapy in Relapsed/Refractory Acute Myeloid Leukemia (AML): Early Results
Authors: Rebecca B Klisovic, Hongyan Wang, Alison Walker, Katherine Walsh, Sumithira Vasu, Ramiro Garzon, Steven M. Devine, Jiang Wang, Celia Garr, Adam Norris, John C. Byrd, Michael R. Grever, William Blum, Kenneth K. Chan, Guido Marcucci
Journal: Blood (2012)