tbuckley/cabot-search huggingface dataset:
Combination Approved for Advanced Multiple Myeloma
Authors: Rebecca Voelker
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance
Authors: Helen R. Stagg, Graham H. Bothamley, Jennifer A. Davidson, Heinke Kunst, Maeve K. Lalor, Marc C. Lipman, Miranda G. Loutet, Stefan Lozewicz, Tehreem Mohiyuddin, Aula Abbara, Eliza Alexander, Helen Booth, Dean D. Creer, Ross J. Harris, Onn Min Kon, Michael R. Loebinger, Timothy D. McHugh, Heather J. Milburn, Paramita Palchaudhuri, Patrick P.J. Phillips, Erik Schmok, Lucy Taylor, Ibrahim Abubakar
Journal: European Respiratory Journal (2019)

2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance.This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence).Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42).In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations.
Recurrence rates of cutaneous SCC of the head and neck after surgery
Authors: C.B. Lee, B.M. Roorda, M. Wakkee, Q. Voorham, A.L. Mooyaart, H.C. Vijlder, T. Nijsten, R.R. Bos
Journal: British Journal of Dermatology (2019)

Squamous cell carcinoma (SCC) is the second most common type of skin cancer in the UK, affecting 10,000 people in England and Wales alone. The risk factors include prolonged sun or tanning bed exposure, having fair skin, older age and having a family member who has had the condition. It is a slow growing cancer involving the outer layer of the skin but can spread to other areas of the body if untreated. SCCs are treated by removing them and this is usually through surgery, but in milder cases freezing and creams are sometimes used. This study was based in the Netherlands looking back at 579 patients with SCC, comparing the rates of cancer returning after undergoing two different forms of surgical treatment. 292 patients underwent standard excision, whereby the SCC and a small margin of skin was cut out and sent to the laboratory to confirm diagnosis and check that all of the cancer was removed. The other 380 patients underwent a newer, specialist procedure called Mohs micrographic surgery. This involves cutting the cancer out layer by layer, each time examining the sample under the microscope during the surgery to see how much cancer has been removed. While this is a much longer procedure, the aim is to preserve as much normal skin as possible, which is particularly important on the face for cosmetic reasons. The researchers followed up the group that underwent standard excision after 5‐7 years and found 8% of the SCCs had returned. In comparison, in the group who had Mohs surgery, only 3% of SCCs came back after 4‐9 years. In total, more SCCs came back in the group having standard excision. Adjusting for the size and depth of the cancer, it can be concluded that patients were three times less likely to have their SCC return if they had Mohs surgery in comparison to standard excision.
Practice Patterns and Outcomes Among Patients With N0M0 Prostate Cancer and a Very High Prostate-Specific Antigen Level
Authors: Vinayak Muralidhar, Paul L. Nguyen, Brandon A. Mahal, David D. Yang, Kent W. Mouw, Brent S. Rose, Clair J. Beard, Jason A. Efstathiou, Neil E. Martin, Martin T. King, Peter F. Orio
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Management of patients with a very high prostate-specific antigen (PSA) level (≥98.0 ng/mL) but clinically localized (N0M0) prostate cancer is challenging. This study sought to determine practice patterns and outcomes among these patients. Patients and Methods: A total of 748,825 patients with prostate cancer from 2004 through 2012 were identified using the National Cancer Database. These patients were subdivided by PSA level (0–9.9, 10.0–19.9, 20.0–39.9, 40.0–59.9, 60.0–79.9, 80.0–97.9, and ≥98.0 ng/mL), nodal status (N0 vs N1), and distant metastases (M0 vs M1). Rates of locoregional treatment and 5-year overall survival (OS) in each group were determined. Survival was compared using Cox regression after adjusting for multiple patient-specific factors. Results: The rate of locoregional treatment for patients with N0M0 disease and PSA level ≥98.0 ng/mL was significantly lower than for those with N1M0 disease (52.6% vs 60.4%; P &lt;.001) or N0M0 disease and PSA level &lt;98.0 ng/mL (52.6% vs 86.6%; P &lt;.001). The 5-year OS rate was similar for patients with N1M0 disease and those with N0M0 disease and a very high PSA level (63.2% vs 59.1%; adjusted hazard ratio [aHR], 0.91; P =.063). The survival benefit associated with locoregional treatment was higher among those with N0M0 disease and a very high PSA level than among those with N1M0 disease (aHR, 0.28 vs 0.44; P &lt;.001). Conclusions: Patients with clinical N0M0 disease and a very high PSA level (≥98.0 ng/mL) have outcomes similar to those with N1 disease but receive locoregional treatment at a lower rate. Future work is needed to investigate the utility of locoregional treatment in this population.
Acquired and inherited risk factors for the developing of venous thromboembolism in cancer patients receiving adjuvant chemotherapy: A prospective trial
Authors: R. Labianca, M. Mandalà, S. Barni, A. Falanga
Journal: Journal of Clinical Oncology (2009)

9572 Background: To assess the thrombogenic role of adjuvant chemotherapy, following radical surgical resection, in ambulatory cancer patients, is of particular interest, because of the little or no tumor burden. The relation between adjuvant chemotherapy and thrombosis has been investigated in breast cancer. Limited information is available in GI cancers. Aim of this study was to investigate the acquired and inherited risk factors for VTE and the incidence of symptomatic VTE in patients on adjuvant chemotherapy for breast or GI cancer. Methods: In a prospective observational study (January 2003 and February 2006), 199 GI (82F/117M; age range, 26–84 years) and 182 breast (180F/2M; age range, 29–85 years) cancer patients were enrolled and followed-up for symptomatic VTE during adjuvant chemotherapy. We prospectively evaluated the effect of acquired (i.e. age, chemotherapy, tumor hystotype, history of thrombosis, body mass index and smoke) and inherited risk factors (i.e. antithrombin, protein C, protein S, homocysteine, activated protein C [APC] resistance, factor V Leiden [FVL] and Prothrombin [PT] mutations). Results: Overall 30 VTE events (7.87%) were recorded: 28 (7.35%) during treatment and 2 (0.52%) during the subsequent follow-up. Among all the 381 cancer patients, FVL was detected in 14 cases (3.67%) and PT mutation in 10 cases (2.62%). At multivariate analysis thrombocytosis (HR 2.8; 95% CI, 1.13–7.30, P&lt; 0.026) and a previous episode of thrombosis (HR 12.4; 95% CI, 2.48–62.6, P&lt; 0.0026) were significantly associated to the development of VTE . There was no association between the FVL or PT mutations and the risk of VTE. Conclusions: Our data demonstrate that, in the adjuvant setting, most VTE occur during therapy. Thrombocytosis prechemotherapy and an history of VTE strongly predict the developing of VTE in the adjuvant setting. No significant financial relationships to disclose.
Increased risk of second primary hematologic and solid malignancies in patients with mycosis fungoides: A Surveillance, Epidemiology, and End Results analysis
Authors: Amrita Goyal, Daniel O'Leary, Kavita Goyal, Nathan Rubin, Kimberly Bohjanen, Maria Hordinsky, Steven T. Chen, Georgios Pongas, Lyn M. Duncan, Aleksandr Lazaryan
Journal: Journal of the American Academy of Dermatology (2019)
Ipilimumab use in a named-patient program in metastatic melanoma: Experiences in 185 German patients.
Authors: Christoph Eichhorn, Max Schlaak, Jessica C. Hassel, Carmen Loquai, Ingo Stoffels, Ralf Gutzmer, Sylvie Paetzold, Ulrich Keller, Jens Ulrich, Athanasios Tsianakas, Friederike Egberts, Eva Janssen, Claus Garbe, Thomas K. Eigentler
Journal: Journal of Clinical Oncology (2012)

e19031 Background: The monoclonal antibody ipilimumab (ipi) showed a survival benefit in patients (pts) with unrespectable metastatic melanoma leading to its approval in 2011. Methods: Ipi was available in Germany before its approval in a Named-Patient Program for pts with unrespectable stage IV/IIIC melanoma. Pts were eligible if they failed at least one prior systemic treatment or were intolerant and did not suffer from auto-immune diseases. Ipi was administered at a dosage of 3mg/kg iv (4 cycles, q21). A re-induction was possible in case of progressive disease after initial clinical benefit. Results: Data from 185 pts (114 male; 71 female, median age: 60 [18-88Y]) of 12 German centers was evaluable. 175 pts actually received ipilimumab (100 pts received all 4 cycles). Reasons for early termination were: Reduced general condition (44%), tumor progression (28%), toxicity or wish of pts (11% each), and incompliance (6%). Response was evaluable in 161 pts. Objective response was observed in 17 pts (1 CR+16 PR), SD in 19 pts (disease control rate 22%). PD was diagnosed in 125 pts. Responding pts were characterized by less organs involved (p=0.028). Median survival for all pts was 8.1 months, 1-year overall survival was 36.4%. Median survival is not yet reached for pts with disease control (94% alive at last observation), whereas it was 5.5 for pts with PD (40% alive at last observation). Treatment was generally well tolerated. Severe (Grade 3+4) auto-immune related toxicities were diarrhea (15 pts), skin rash (1 pt) and hepatitis (1 pt). Aseptic meningitis was observed in 1 pt; and hypophysitis (Grade 2) likewise in 1 pt. Conclusions: Data coming from these 161 patients appear to be consistent with safety and efficacy profiles determined in large clinical trials. Tumor responses were induced in a subset of pts and associated with prolonged survival.
<i>BRAF</i> mutation testing with a novel, rapid, fully automated molecular diagnostics prototype platform.
Authors: Helen J. Huang, Benoit Devogelaere, Gerald Steven Falchook, Siqing Fu, Laura S. Angelo, David S. Hong, Sarina Anne Piha-Paul, Aung Naing, Veronica R. Holley, Apostolia Maria Tsimberidou, Vanda M. T. Stepanek, Kevin Kim, Vivek Subbiah, Jennifer J. Wheler, Ralph Zinner, Robert A. Wolff, Erwin Sablon, Geert Maertens, Razelle Kurzrock, Filip Janku
Journal: Journal of Clinical Oncology (2013)

11086 Background: Mutations in the BRAF gene provide actionable targets for cancer therapy in melanoma and other tumor types. Novel, fast, and accurate diagnostic systems are needed for further implementation of personalized therapy. Methods: The molecular diagnostics (MDx) prototype platform (Biocartis, Mechelen, Belgium) is a fully integrated real-time PCR-based system with high sensitivity (1% mutant in wild-type [wt] background) and fast turnaround time (&lt; 90 minutes), which requires no sample preparation and &lt;2 min hands-on time. Archival formalin-fixed paraffin-embedded tumor samples (1 to 5 shavings of 10 µm) from patients (pts) with advanced cancers previously tested for V600 BRAF mutations in a CLIA-certified Molecular Diagnostic Laboratory (PCR-based sequencing or Sequenom MassARRAY) were tested for BRAF V600 mutations using the MDx prototype platform. Concordance between methods and treatment outcomes with BRAF/MEK inhibitors were analyzed. Results: Forty-seven pts (melanoma, n=26; colorectal, n=8; papillary thyroid, n=3; other cancers, n=10) with available tissue and CLIA laboratory BRAF results were selected (BRAF V600 mutant, n=37; BRAF V600 wt, n=10). Of the 40 pts for whom the same tissue block was used for MDx and CLIA, BRAF status was concordant in 38 (95%; kappa 0.87; 95% CI 0.69-1.05) of them. BRAF status by MDx was discordant with CLIA in 3 of 47 cases (mutant by CLIA, but not MDx); one discrepant case contained a different mutation subtype (resp. V600E vs. V600K/R), and in another case different tissue blocks were used for MDx vs. CLIA testing. Of 34 pts with BRAF mutations detected by MDx, 28 were treated on protocols (on the basis of the CLIA results) with BRAF/MEK inhibitors and 8 (29%) had a partial (n=7) or complete response (n=1). Of interest, 1 pt with prostate cancer (V600E by CLIA, wt by MDx) received a BRAF/MEK inhibitor and did not respond. Detailed patient characteristics, mutation types and discrepancy analysis will be presented. Conclusions: The BRAF V600 mutation MDx prototype assay is a fast (turn-around time about 1.5 hours) and simple (&lt;2 minutes hands-on time) test to determine BRAF mutation status with 95% concordance with CLIA laboratory if identical tissue blocks are used.
PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN
Authors: Abdallah Flaifel, Wanling Xie, David A. Braun, Miriam Ficial, Ziad Bakouny, Amin H. Nassar, Rebecca B. Jennings, Bernard Escudier, Daniel J. George, Robert J. Motzer, Michael J. Morris, Thomas Powles, Evelyn Wang, Ying Huang, Gordon J. Freeman, Toni K. Choueiri, Sabina Signoretti
Journal: Clinical Cancer Research (2019)

Programmed death-ligand 1 (PD-L1) status by IHC is prognostic in metastatic renal cell carcinoma (mRCC), and its role as a potential predictive biomarker is under investigation. Using tumor tissue from the METEOR (NCT01865747) and CABOSUN (NCT01835158) clinical trials, we explored whether PD-L1 expression and the extent of the immune cell infiltrate can serve as prognostic and/or predictive biomarkers for cabozantinib and other targeted agents.IHC double staining for PD-L1 and CD45/CD163 (immune cell markers) was performed on tumor tissue from METEOR (n = 306) and CABOSUN (n = 110) clinical trials. Immune cell density and MET expression levels were also analyzed. Our primary aim was to correlate progression-free survival (PFS) by independent central review with PD-L1 status in patients treated with cabozantinib, everolimus (METEOR), or sunitinib (CABOSUN). Overall survival (OS) was also interrogated.Tumor cell (TC) PD-L1 expression (≥1% cutoff) was detected in 29% and 23% of tumors from patients in the METEOR and CABOSUN trials, respectively. On univariate analysis, patients with PD-L1-positive TC had poorer PFS and OS than patients with PD-L1-negative TC on both trials, independent of therapy. On multivariable analysis and when combining the two trials, the association between TC PD-L1 expression and OS was statistically significant for all patients (P = 0.034) and for patients treated with cabozantinib only (P = 0.038). Cabozantinib was associated with improved PFS (HR < 0.70) and OS (HR < 0.85) compared with everolimus and sunitinib irrespective of PD-L1 expression.Higher PD-L1 expression results in worse clinical outcomes in mRCC treated with targeted therapy. Furthermore, PD-L1 expression is not predictive of response to cabozantinib therapy.
Disease-driven symptoms and response to chemotherapy in treatment-naive patients with advanced non-small cell lung cancer (NSCLC).
Authors: Desiree Jones, Elisabeth G. Vichaya, Xin Shelley Wang, Tito R. Mendoza, Gary M. Mobley, Charles Lu, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2012)

9118 Background: The disease-driven symptoms of treatment-naïve patients with advanced NSCLC have not been the primary focus of previous studies. One reason for this gap in the literature is that randomized trials typically lack an opportunity to capture the symptom profiles of patients who are truly treatment-naïve. To address this need, this study sought to: (i) characterize the symptom profile of treatment-naïve patients with advanced NSCLC, and (ii) describe patients’ response to chemotherapy. Methods: The study sampleconsisted of43 treatment-naïve patients (no prior treatment by surgery, radiation, or chemotherapy) with a primary diagnosis of advanced NSCLC from the MD Anderson Cancer Center, and was derived from a larger study (Cleeland et al. J Clin Oncol 29:2859-65, 2011). Patients’ symptoms were assessed pre-chemotherapy, and then prospectively at 6, 12, and 18 weeks from initiation of chemotherapy using the MD Anderson Symptom Inventory Lung Cancer module. Results: The top symptoms reported by patients, in order of severity, were shortness of breath, fatigue, distress, sadness, drowsiness, and pain. Chemotherapy did not significantly improve shortness of breath, drowsiness, pain, disturbed sleep, lack of appetite, coughing, and constipation in this sample of patients, and was associated with a significant increase in levels of fatigue and numbness (mean difference in fatigue at 12 weeks from baseline = 2.8; 95% CI, 0.5–2.9; p = .01; and in numbness from baseline = 1.1; 95% CI, 0.2–2.0; p = .02). Conclusions: This study characterizes the disease-driven symptoms of truly treatment-naïve patients with advanced NSCLC. Knowledge of these symptoms is of intrinsic value in the clinical management of advanced NSCLC as it provides the critical reference point against which symptom palliation must be measured. Patients’ lack of symptomatic improvement from chemotherapy in this study suggests that this sub-set of patients may have had rapidly progressing disease and that chemotherapy may have prevented symptoms levels from worsening. Consistent with literature, transient but significant increase in both fatigue and numbness are chemotherapy-related toxicities.
Molecular Staples for Tough and Stretchable Adhesion in Integrated Soft Materials
Authors: Baohong Chen, Jiawei Yang, Ruobing Bai, Zhigang Suo
Journal: Advanced Healthcare Materials (2019)

The integration of soft materials-biological tissues, gels, and elastomers-is a rapidly developing technology of this time. Whereas hard materials are adhered using adhesives of hard polymers since antiquity, these hard polymers are generally unsuited to adhere soft materials, because hard polymers constrain the deformation of soft materials. This paper describes a design principle to use hard polymers to adhere soft materials, such that adhesion remains tough after the adhered soft materials are subject to many cycles of large stretches in the plane of their interface. The two soft materials have stretchable polymer networks, but need not have functional groups for adhesion. The two soft materials are adhered by forming, in situ at their interface, islands of a hard polymer. The adhesion is tough if the islands themselves are strong, and the polymers of the islands are in topological entanglement with the polymer networks of the soft materials. The adhesion is stretchable if the islands are smaller than the flaw sensitivity length. Several methods of forming the hard polymer islands are demonstrated, and the mechanics and chemistry of adhesion are studied. The design principle will enable many hard polymers to form tough and stretchable adhesion between soft materials.
Monitoring of NK cell activity and serum LDH in metastatic melanoma patients treated with DTIC and interferon-alpha2a, with or without retinoic acid
Authors: G. Konjevic, V. Jovic, A. Vuletic, S. Radulovic, S. Jelic, I. Spuzic
Journal: Journal of Clinical Oncology (2007)

19000 Background: The activity of NK cells, expression of CD69, and serum LDH were evaluated in terms of response to therapy in metastatic melanoma patients. Methods: In phase II clinical study metastatic melanoma (MM) patients were treated with DTIC (800 mg/m 2 , d1) and IFN-alpha 2a (5×10 6 IU/m 2 s.c., d2–6 (group A, n=25) and 28 patients received the same therapy supplemented with RA, 60 mg/d, d1–10 (group B). Before and after each therapy cycle NK cell activity, CD69+NKcells and LDH were monitored in patients and 39 healthy controls. Results: There is no significant difference in OR (group A 32%, B 21%), in time to progression between groups. NK cell activity was significantly decreased pretherapy in both groups, with a significant increase in the 1st cycle in both groups. NK cell activity did not show significant correlation with OS in group A compared to group B (p=0.445). 20% of patients in group A with pretherapy NK cell cytotoxicity above 30% had better survival from month 3 to 12 of follow-up and a longer maximal survival (1.2 vs. 1.0 year, respectively). In comparison to pre-therapy values, all responding MM patients had a significantly higher increase of CD69 expression on CD56+ NK cells, while the increase was only significantly higher in responders in group B. Analyses of serum LDH level show a significantly higher time and therapy cycle-dependent decrease in group A compared to group B (50% vs. 25%, respectively). However, it is shown that responders in group B had a significantly greater decrease in serum LDH level compared to responders in group B (70% vs. 20%, respectively), if the level after a cycle was evaluated in terms of pretherapy values, as well as a greater decrease if the evaluation in each cycle was done compared to each pretherapy value (35% vs. 20%, respectively). Conclusions: Even though there is no significance in clinical response between patients in group A and B, in agreement with a steady-state pattern of NK cell activity, the fact that only responders in group B had a significant increase in CD69 expression on CD56+ NK cells, as well as the finding that the decrease in serum LDH was significantly greater in patients in group B, implicates favorable imunopotentiating and antitumor effect of RA in the therapy of metastatic melanoma. No significant financial relationships to disclose.