tbuckley/cabot-search huggingface dataset:
EGFR mutations in lung adenocarcinoma: Epidemiology and clinical relevance of common versus rare mutations.
Authors: Zoltan Lohinai, Gyula Ostoros, Katalin Fabian, Tamas Barbai, Erzsebet Raso, Jozsef Timar, Ilona Kovalszky, Anita Rozsas, Viktoria Laszlo, Mir Alireza Hoda, Michael Grusch, Walter Berger, Walter Klepetko, Judit Moldvay, Balazs Dome, Balazs Hegedus
Journal: Journal of Clinical Oncology (2014)

e19067 Background: In lung adenocarcinoma, oncogenic mutations of the epidermal growth factor receptor (EGFR) are the most frequent and biologically targetable molecular alterations. Classical activating mutations of exon 21 (L858R) and exon 19 deletions serve as positive predictive markers for EGFR tyrosine kinase inhibitors (TKIs). However, there are several rare mutations in the EGFR gene with unknown influence on TKI response. Methods: A cohort of 814 lung adenocarcinoma patients treated at the National Koranyi Institute for TB and Pulmonology and at the Department of Pulmonology, Semmelweis University between January 2010 and March 2013 were included. All patients underwent KRAS (codon12 and 13) and/or EGFR (exons 18-21) analyses for TKI therapy indication. Clinical follow-up data was collected for 645 patients. Results: Among the 814 cases we found 480 (59%) KRAS and EGFR wild-type, 216 (27%) KRAS mutant, 42 (5%) classical EGFR mutant and 49 (6%) rare EGFR mutant cases and 27 (3%) synonymous EGFR mutations or SNPs. Univariate analysis identified gender, ECOG performance status (PS), smoking status, disease stage and EGFR mutation as significant prognostic factors (p=0.016; p<0.001; p=0.028; p=0.006; p<0.001, respectively). Rare EGFR - as opposed to classical mutations - appeared to be associated with smoking (p<0.001). In regards to TKI therapy, irrespective of treatment lines, patients harboring classical EGFR mutations had significantly better response rate (71% vs. 37 %, p=0.039) and longer progression-free survival (median PFS 6.2 vs. 12 months, p=0.076) than those with rare mutations. When patients with classical EGFR mutations together with activating rare mutations (G719 and L861) were compared to the remaining cases with rare mutations, the effect on PFS reached significance (p=0.031). Conclusions: Classical and rare EGFR mutations showed distinct epidemiological and TKI therapy related properties in this retrospective study. Our findings suggest that additional studies characterizing the TKI sensitizing status of individual rare mutations are needed to optimize EGFR targeted therapy in lung adenocarcinoma.
USE OF THE METRIC SYSTEM
Journal: JAMA (1953)

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 Journals 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 2024 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
The effect of raloxifene hydrochloride for the prevention of health care problems of patients who underwent surgeries for endometrial cancer: A multicenter clinical trial.
Authors: Koji Nakamura, Kenjiro Sawada, Michiyo Sugiyama, Seiji Mabuchi, Takeshi Hisamatsu, Yukihiro Nishio, Kimihiko Ito, Ken-ichirou Morishige, Tadashi Kimura, Shoji Kamiura
Journal: Journal of Clinical Oncology (2014)

5602 Background: The removal of ovaries is necessary at the surgery for endometrial cancer. However, since the loss of ovaries cause several health problems in patients, the establishment of the prevention therapy after surgeries should be required. We conducted a multicenter clinical trial and assessed the effect of raloxifene on bone mineral density (BMD), bone metabolism and lipid profile of the patients who underwent surgeries for endometrial cancer. Methods: 77 women were enrolled after their surgeries. After a written informed consent, participants were randomized into two groups: group I; 39 women received alfacalcidol (1 μg/day) alone and group II; 38 received the study drug, raloxifene hydrochloride, at a dose of 60 mg/day with alfacalcidol. All patients received supplemental calcium 1.2g/day. BMD, serum bone markers (NTx and BAP) and lipid profiles were evaluated at the enrollment, 6, 12, and 24 months after the enrollment. Results: 64 (83%) finished 24-month follow-up. No significant differences between the groups were seen in the baseline data. At 24 months, lumbar and femoral neck BMD were significantly increased in group II compared with group I (3.0% vs -0.8% (p=0.009), +2.0% vs -2.8% (p=0.003)). In group II, values of total cholesterol as well as LDL-cholesterol were significantly reduced by 8.4% (p=0.0006), 14.9% (p<0.0001), whereas in group I, no significant reduction were seen. In group II, both serum NTX and BAP values were significantly reduced by 16.1% (p=0.0006), 24.7% (p<0.0001). Recurrence was found in two (2.6%) case in group I and no severe adverse events were noted in any cases throughout the study period. In sub-analyses, the patients who received chemotherapy showed significantly higher response to raloxifene. Conclusions: The treatment of raloxifene to the patients after surgeries not only significantly increased lumbar and femoral neck BMD, but decreased serum bone markers as well as total and LDL-cholesterol values with safety profiles. It suggests that raloxifene could constitute a good therapeutic option to improve the health care problems of the patients with endometrial cancer after surgeries. Clinical trial information: UMIN000013039.
Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: a cohort study
Journal: The Lancet Global Health (2016)

Sepsis is one of the most common causes of neonatal deaths globally. Most sepsis-related deaths occur in low-income and middle-income countries, where the epidemiology of neonatal sepsis remains poorly understood. Most of these countries lack proper surveillance networks, hampering accurate assessment of the burden of sepsis, implementation of preventive measures, and investment in research. We report results of neonates born in hospital from a multicentre collaboration on neonatal sepsis.In this cohort study, dedicated research teams prospectively followed up neonates born in one of three tertiary care centres in Delhi, India (Vardhaman Mahavir Medical College, Maulana Azad Medical College, and All India Institute of Medical Sciences [coordinating centre]) and subsequently admitted to the intensive care unit. Neonates were followed up daily until discharge or death. On clinical suspicion, neonates underwent sepsis work-up including blood cultures. The isolated organisms were identified and tested for antimicrobial susceptibility. We defined Gram-negative isolates resistant to any three of five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) as multidrug resistant.13 530 neonates of 88 636 livebirths were enrolled between July 18, 2011, and Feb 28, 2014. The incidence of total sepsis was 14·3% (95% CI 13·8-14·9) and of culture-positive sepsis was 6·2% (5·8-6·6). Nearly two-thirds of total episodes occurred at or before 72 h of life (defined as early onset; 1351 [83%] of 1980). Two-thirds (645 [64%]) of 1005 isolates were Gram-negative including, Acinetobacter spp (22%), Klebsiella spp (17%), and Escherichia coli (14%). The pathogen mix in early-onset sepsis did not differ from that of late-onset sepsis (ie, after 72 h). High rates of multidrug resistance were observed in Acinetobacter spp (181/222, 82%), Klebsiella spp (91/169, 54%), and Escherichia coli (52/137, 38%) isolates. Meticillin resistance prevailed in 61% (85/140) of coagulase-negative staphylococci and 38% (43/114) of Staphylococcus aureus isolates. Nearly a quarter of the deaths were attributable to sepsis. The population-attributable risks of mortality were 8·6% in culture-negative sepsis, 15·7% in culture-positive sepsis by multidrug-resistant organisms, and 12·0% in culture-positive sepsis by non-multidrug-resistant organisms.The high incidence of sepsis and alarming degree of antimicrobial resistance among pathogens in neonates born in tertiary hospitals underscore the need to understand the pathogenesis of early-onset sepsis and to devise measures to prevent it in low-income and middle-income countries.Indian Council of Medical Research.
Enzalutamide activity in patients with metastatic castration resistant prostate cancer (mCRPC) previously responding to antiandrogen withdrawal syndrome (AWS): A preliminary report.
Authors: Sergio Bracarda, Giuseppe Procopio, Daniele Alesini, Francesco Grillone, Francesco Massari, Alberto Zaniboni, Rodolfo Mattioli, Sebastiano Buti, Enrico Garanzini, Michele Sisani, Alketa Hamzaj, Amelia Altavilla, Verena De Angelis
Journal: Journal of Clinical Oncology (2014)

e16058 Background: AWS is defined as decline in PSA after withdrawal of an antiandrogen (AA) during maximum androgen blockade and it has been described in less than 20% of mCRPC patients. The most likely mechanism of action for AWS is a switch of an AA from antagonistic to agonistic activity on androgen receptor. At the best of our knowledge, no data exist regarding a possible interactions between a previous AWS and the following efficacy of the second generation AA Enzalutamide (ENZ), recently approved for mCRPC patients after docetaxel failure.Methods: We retrospectively identified all consecutive patients with mCRPC progressing on or after docetaxel who were treated with ENZ at 8 Italian centers within a named patient program. AWS was defined as a PSA response after 4-6 weeks from flutamide or bicalutamide withdrawal. ENZ activity was evaluated by biochemical and/or objective response and duration of response, calculated as the time (in months) from initial response to documented tumor progression or death from any cause. Correlation between AWS and ENZ activity has been evaluated using non-parametric tests.Results: 93 patients have been analyzed. AWS was evaluable in 52 (57%). Median age was 72.2, median Gleason score (GS) was 8.0. AWS was present in 6/52 patients (11.5%) while 22/52 were evaluable for both the presence of AWS and response to ENZ. Patients with AWS were older than patients with no AWS (76.0 vs 71.4, p=,327), had a lower GS (8.0 vs 7.0, p=,111) and had a longer duration of response to ENZ (7.0 vs 4.0 months, p=,043). These data were confirmed by a non-parametric Mann-Whitney test (p=,025). A trend in biochemical and objective response was also observed in these patients. Conclusions: This preliminary case series represents the first report of a correlation between AWS with first generation AA and response to ENZ in mCRPC patients. Our data, suggesting a direct correlation between presence of AWS and duration of response to ENZ, warrant further prospective validation.
Immune status of patients with ovarian cancer of III-IV stages after using of interferon-gamma (ingaron) in complex treatment.
Authors: Anna Yurevna Ardzha, Galina Andreevna Nerodo, Elena Yurievna Zlatnik, Andrey Vladimirovich Bakhtin, Elina T Mkrtchyan, Anna Petrovna Menshenina
Journal: Journal of Clinical Oncology (2014)

e22092 Background: The aim of the study is the assessment of immune status of patients with ovarian cancer after using of interferon-gamma (Ingaron) in complex treatment. Methods: The material of the study was represented by data about 54 patients with III-IV stages of ovarian cancer aged 34 – 77 years. Patients were divided into 2 groups: the main one (n=28) subjected to neoadjuvant chemotherapy with the using of interferon-gamma (Ingaron) and the control one (n=26) subjected to CAP chemotherapy withoutIngaron. The regimen of chemoimmunothepary was the following: on the 1, 2, 3, 5 days 500 000 IU/m2 of Ingaron was administrated intramusculary; on the 4th day CAP chemotherapy (cisplatin 75-100 mg/m2, cyclophosphamide 400-600 mg/m2 ,doxorubicin 40-50 mg/m2) was carried out. Patients` immune status was studied before and in dynamics of treatment (after neoadjuvant course, after surgery and during postoperative courses) by means of flow cytometry onBD CantoII and the panel of Т, В, NK-monoclonal antibodies (CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD16+CD56+). Results: In patients treated with the use of Ingaron positivedynamics of immune status was observed: the increase of total T-lymphocytes` (from 69.5±3.1 to 78.8±2.6%) and of CD3+CD4+ (from 39.2±3.37 to 52.4±5.0%) amounts was noted in all of the steps of treatment, the most significant after surgery. Using of chemotherapy without Ingaron caused no immunologic changes; besides the CD3+ and CD3+CD4+cells` levels were lower than in the patients of the main group (70,1±2,9 and 39,2±4,4% respectively, Р<0,05). Conclusions: Using of interferon-gamma (Ingaron) in complex treatment of patients with ovarian cancer produces significant improvement of some important factors of cellular immunity.
Abstract 121: Outcome Of Patients With Kawasaki Disease Treated With Intravenous Pulse Methylprednisolone As Primary Therapy: An 8 Year Single Center Experience
Authors: Christine B Bernal, Charles Cuaso, Joenavin Ngo
Journal: Circulation (2015)

Kawasaki disease (KD) is a medium vessel vasculitis with predilection to affect the coronary arteries. While intravenous immunoglobulin (IVIG) remains the standard primary treatment, the cost remains a big burden for parents of patients in developing countries. Steroids do have a role in IVIG-resistant KD but studies on its benefit in addition to IVIG as primary treatment are conflicting. In our institution, parents who cannot afford IVIG consented to intravenous pulse methylprednisolone (IV MP) as an alternative primary treatment. Objective: To review the outcome of KD patients treated with IV MP as primary treatment. Methods: Retrospective chart review of patients who fulfilled the diagnostic criteria for KD and treated with IV MP (30 mg/kg/dose, maximum of 1 gm/dose, given once daily for 3 consecutive days) plus high dose Aspirin from January 2006 to December 2013. Results: A total of 36 patients were included in the study with a mean age of 4.2 years (range 0.4-12.6). The F:M ratio was 1:1. Majority (75% - 27/36) of the patients received the treatment before the tenth day of illness. There was clinical improvement in all patients with lysis of fever and resolution of all signs and symptoms immediately after the first dose of IV MP. None of the patients had a relapse of KD. The CRP significantly decreased after the treatment in all patients. For all patients, baseline echocardiography was done by a single pediatric cardiologist and was repeated after 2 months, 6 months, then yearly. At baseline, 36 patients had pericardial effusion, 13 with perivascular brightness, 15 with coronary ectasia and 8 with valvular abnormalities (MR, AR, TR). Follow up evaluation after 2 months showed no echocardiographic abnormalities in all patients, up until the yearly echo. None of the patients developed coronary aneursysm. There was no reported immediate nor long term side effects from the steroid therapy. Conclusion: Intravenous methylprednisolone is effective in controlling the clinical manifestations of KD and in preventing cardiac complications. It is safe and well-tolerated by patients. It can be an alternative first line treatment for KD patients whose parents cannot afford the high cost of IVIG.
Validity of the chemotherapy-induced peripheral neuropathy self-check sheet.
Authors: Masaya Inoue, Yumiko Miyoshi, Chie Onishi, Mifumi Fujie, Naomi Senoo, Satoshi Kumanomido, Koshi Kawakami, Ichiro Moriyama, Ritsuko Wakatsuki, Junji Suzumiya
Journal: Journal of Clinical Oncology (2014)

e20719 Background: Chemotherapy-induced peripheral neuropathy (CIPN) ismajor dose-limiting factors for some anti-cancer drugs and it makes against cancer patients’ benefit. However, it is frequently difficult to evaluate the severity of CIPN for medical staffs. We tried to develop a questionnaire for accurate evaluation for CIPN, and compared newly developed questionnaire of CIPN with that of free-style interviews. Methods: We developed the CIPN self-check sheet by evaluating the existing self-assessment tools for CIPN and matching the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grades. 77 cancer patients participated in this study from August to December 2011. To evaluate the validity of the newly developed CIPN self-check sheet compared with a free-style interview assessment, the cross-classification and κ coefficients between the CTCAE grades from each assessment and those from a comprehensive assessment were analyzed. The comprehensive assessment utilized information from the medical examination, the free-style interview, and the CIPN self-check sheet. Results: 248 CIPN self-check sheets were obtained from cancer patients (median number of sheets per patient, 3; range, 1-14). The cross-classification analysis illustrates that the CIPN self-check sheet successfully identified all of grade 3 cases. The coefficient of the CIPN self-check sheet was significantly higher comparing with that of the free-style interviews. [The κ values were 0.988 (P<0.01) and 0.501 (p<0.01) for the self-check sheet and interviews, respectively.] Conclusions: The newly developed CIPN self-check sheet is useful to evaluate the severity of CIPN based on CTCAE grades more accurately than the free-style interviews.
A four-arm randomized phase II trial with NGR-hTNF given at low or high dose with or without doxorubicin in soft tissue sarcomas (STS).
Authors: Stefano Ferrari, Paolo G Casali, Jean-Yves Blay, Axel Le Cesne, Tonini Giuseppe, Nasim Ali, Vittorio Perfetti, Emanuela Palmerini, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2014)

10525 Background: NGR-hTNF, a tumor targeted antivascular agent, exhibits a biphasic dose-response curve with activity shown at low dose (LD) or high dose (HD). Vascular effects at LD are driven by early vessel normalization that enhances intratumoral doxorubicin (D) uptake and late vessel damage, while at HD by rapid vessel disruption. Methods: Advanced STS patients (pts), stratified by prior D dose (> or ≤ 300 mg/m2), were randomly assigned to receive NGR-hTNF alone at LD (0.8 μg/m2/d1/q1w) in arm A or at HD (45 μg/m2/d1/q1w) in arm B, or with D (60 mg/m2/d1/q3w) at LD in arm C and at HD in arm D. Progression free survival (PFS) was primary endpoint with tumor assessment done q6w until progressive disease (PD). Using a 2-stage design, each regimen was rejected if ≤2/14 and ≤7/24 pts were PD free at 3 months after 1st and 2nd stage, respectively (β=20%; α=10%; n=96). Secondary aims: adverse events (AEs), tumor response by RECIST criteria and early metabolic response (MR), quantified by fractional changes in SUV using FDG-PET according to EORTC criteria Results: In all, 69 pts (median age 55 years; men 38; PS ≥ 1 31; median prior lines 2, range 0-7) received 767 weekly cycles (mean 11; range 1-51). Main grade 3/4 AEs were neutropenia (23%) and chills (7%). Primary endpoint was met only for arm C (LD NGR-hTNF plus D), with 7/14 and 15/28 pts PD free at 3 months after 1st and 2nd stage, respectively. Median PFS was 1.3 months (95% CI, 1.1-1.5) for arm A, 1.5 (1.1-1.9) for B, 3.6 (2.3-4.9) for C and 1.4 (0.9-1.9) for D (p=0.005 for trend). As best response per RECIST, 28 (45%) of 62 evaluable pts had stable disease (SD): 1/12 in arm A, 6/12 in B, 17/26 in C (median length 4.3 months; range 2.9-23.2) and 4/12 in D. In arm C, median PFS was 2.9 and 4.3 months for naive and pretreated pts, respectively, while median OS was 9.8 months (HR=0.46 vs other pooled arms; p=0.01). By PET imaging done at 3 weeks, 10 (23%) of 43 assessable pts had partial MR (5 SD/5 PD per RECIST), with mean change in SUV of -37% (±12), 25 pts stable MD (8 SD/17 PD) and 8 progressive MD (5 SD/3 PD). PET sensitivity in predicting PD or non-PD per RECIST was 12% and 72%, respectively. Conclusions: LD NGR-hTNF plus D shows safe and favourable clinical activity particularly in pretreated STS. Clinical trial information: NCT00484341.
NKG2D-CAR Transduced Primary Natural Killer Cells Efficiently Target Multiple Myeloma Cells
Authors: Alejandra Leivas, Paula Rio, Rebeca Mateos, Mari Liz Paciello, Almudena Garcia-Ortiz, Lucia Fernandez, Antonio Perez-Martinez, Dean Anthony Lee, Daniel J. Powell, Antonio Valeri, Joaquin Martinez-Lopez
Journal: Blood (2018)
Impact of recent clinical trials on the use of chemotherapy for resectable non-small cell lung cancer in the United States.
Authors: Ravi Rajaram, Jennifer Leigh Paruch, Jane Louise Holl, Clifford Y. Ko, David Porter Winchester, Karl Y. Bilimoria, Jyoti D. Patel, Malcolm M. DeCamp
Journal: Journal of Clinical Oncology (2014)

6619 Background: Multiple clinical trials have demonstrated chemotherapy combined with surgery improves survival in many patients with non-small cell lung cancer (NSCLC). Per NCCN Guidelines, for selected stage IB and II-IIIA patients there is level 2B and 1 evidence for use of chemotherapy, respectively. We sought to (1) evaluate changes in chemotherapy utilization in surgically treated NSCLC over time and (2) to identify factors predictive of chemotherapy administration in this population. Methods: Patients who had surgery for AJCC seventh edition stage IB-IIIA NSCLC (2002-2011) were identified from the National Cancer Data Base. Administration of chemotherapy (neoadjuvant or adjuvant) was assessed over time. Hierarchical regression models were developed to assess patient, hospital, and tumor characteristics predicting chemotherapy utilization separately for IB and II-IIIA tumors. Results: Overall, 112,049 patients had resection for stage IB-IIIA NSCLC. In 55,016 patients with stage IB disease, chemotherapy use increased from 5.3% to 15.1%, with adjuvant therapy specifically increasing from 2.4% to 14.4% (both p < 0.01). On multivariable analysis, stage IB patients were less likely to receive chemotherapy if they were older, treated at an academic or NCI center (vs. community), had more comorbidities, or had lower grade tumors (all p ≤ 0.01). In 57,033 patients with stage II-IIIA disease, chemotherapy administration also significantly increased from 29.3% to 58.4%, with adjuvant therapy increasing from 18.0% to 43.4% (both p < 0.01). Predictors of decreased chemotherapy use in stage II-IIIA patients included increasing age, non-private insurance status, non-NCI academic treating facility, increased comorbidities, squamous histology, lower grade tumors, or sublobar resection (all p < 0.04). Stage IIIA (vs. IIA) disease (OR 2.82, 95% CI 2.56-3.11) was predictive of increased chemotherapy delivery. Conclusions: In patients with resected stage IB-IIIA NSCLC, use of chemotherapy has substantially increased since 2002. However, while many providers have adopted evidence-based recommendations into their practice, sizeable treatment gaps persist and are areas for targeted quality improvement.