117 research outputs found
Response assessment in metastatic melanoma treated with ipilimumab and bevacizumab: CT tumor size and density as markers for response and outcome
A case of type 1 facioscapulohumeral muscular dystrophy (FSHD) with restrictive ventilatory defect and congestive heart failure
[Background] Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease characterized by asymmetric involvement of muscles in the face, upper extremity, trunk, and lower extremity regions, with variable severity. It was recently reported that restrictive respiratory involvement is more frequent and severe than previously recognized, while cardiac dysfunction other than arrhythmia is still considered extremely rare in FSHD. [Case report] A 59-year-old man presenting with marked muscle atrophy in the trunk and asymmetrical muscle atrophy in the legs was hospitalized because of dyspnea and edema in the face and limbs. Shortness of breath with body movement started from approximately 40 years of age. Muscle biopsy revealed myopathic change with mild to moderate variation in fiber size. The diagnosis of FSHD was made by D4Z4 contraction to three repeats on genetic testing. A pulmonary function test revealed a decline of forced vital capacity (FVC) and a preserved FEV1/FVC indicating restrictive ventilatory defect (RVD). Ultrasonic echocardiogram (UCG) showed diffuse left ventricular hypokinesis, ventricular septum thickening, pericardial effusion, and decreased ejection fraction (LVEF 30%). [Conclusion] Although restrictive ventilatory defect and congestive heart failure are uncommon in FSHD, respiratory and cardiac evaluation may be necessary in patients with FSHD
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Intrathoracic malignant peripheral nerve sheath tumors: imaging features and implications for management
Background: The aim of the study was to analyze the clinical and imaging characteristics of primary intrathoracic malignant peripheral nerve sheath tumors (MPNSTs). Patients and methods. In this institutional review board (IRB)-approved retrospective study, clinical and imaging features of 15 patients (eight men; mean age 50 years [range 18–83)] with pathologically proven malignant peripheral nerve sheath tumors seen from January 1999 to December 2011 were analyzed. Imaging features (CT in 15, MRI in 5 and PET/CT in 4) of primary tumors were evaluated by three radiologists and correlated with clinical management. Results: Of the 15 tumors, six were located in the mediastinum (two each in anterior, middle and posterior mediastinum), four in chest wall, two were paraspinal, and three in the lung. Four patients had neurofibromatosis-1 (NF1); four tumors had heterologous rhabdomyoblastic differentiation (malignant triton tumor). Masses typically were elongated along the direction of nerves, with mean size of 11 cm. The masses were hypo- or isodense to muscles on CT, isointense on T1-weighted images, hyperintense on T2-weighted images and intensely fluorodeoxyglucose (FDG) avid (mean standardized uptake value [SUV]max of 10.5 [range 4.4–23.6]). Necrosis and calcification was seen in four tumors each. Finding of invasion of adjacent structures on imaging led to change in management in seven patients; patients with invasion received chemoradiation. Conclusions: Intrathoracic MPNSTs appear as large elongated masses involving mediastinum, lung or chest wall. Radiological identification of invasion of adjacent structures is crucial and alters therapy, with patients with invasion receiving neoadjuvant or adjuvant chemoradiation
Measurement Variability in Treatment Response Determination for Non-Small Cell Lung Cancer: Improvements using Radiomics
Multimodality imaging measurements of treatment response are critical for clinical practice, oncology trials, and the evaluation of new treatment modalities. The current standard for determining treatment response in non-small cell lung cancer (NSCLC) is based on tumor size using the RECIST criteria. Molecular targeted agents and immunotherapies often cause morphological change without reduction of tumor size. Therefore, it is difficult to evaluate therapeutic response by conventional methods. Radiomics is the study of cancer imaging features that are extracted using machine learning and other semantic features. This method can provide comprehensive information on tumor phenotypes and can be used to assess therapeutic response in this new age of immunotherapy. Delta radiomics, which evaluates the longitudinal changes in radiomics features, shows potential in gauging treatment response in NSCLC. It is well known that quantitative measurement methods may be subject to substantial variability due to differences in technical factors and require standardization. In this review, we describe measurement variability in the evaluation of NSCLC and the emerging role of radiomics. © 2019 Wolters Kluwer Health, Inc. All rights reserved
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Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors
Objectives
The optimal management of locally advanced and metastatic pulmonary carcinoid tumors remains to be determined.
Materials and methods
A retrospective review was conducted on patients with typical and atypical pulmonary carcinoid tumors treated at our institutions between 1990 and 2012.
Results
300 patients were identified with pulmonary carcinoid, (80 patients with atypical carcinoid), of whom 29 presented with metastatic disease (16 atypical). Of evaluable patients, 26 (41%) with stages I–III atypical carcinoid tumors recurred at a median time of 3.7 years (range, 0.4–32), compared to 3 (1%) patients with typical carcinoid (range, 8–12.3). 39 patients were treated with chemotherapy, including 30 patients with metastatic disease (27 atypical), and 7 patients were treated with adjuvant platinum–etoposide chemoradiation (6 atypical, 1 typical, 6 stage IIIA, 1 stage IIB). At a median follow-up of 2 years there were 2 recurrences in the 7 patients receiving adjuvant treatment. Median survival after diagnosis of metastatic disease for patients with atypical pulmonary carcinoid was 3.3 years with a 5-year survival of 24%. Treatment regimens showing efficacy in pulmonary carcinoid include 15 patients treated with octreotide-based therapies (10% response rate (RR), 70% disease control rate (DCR), 15 month median progression-free survival (PFS)), 13 patients treated with etoposide + platinum (23% RR, 69% DCR, 7 month median PFS), and 14 patients treated with temozolomide-based therapies (14% RR, 57% DCR, 10 month median PFS). 8 of 10 patients with octreotide-avid disease treated with an octreotide-based regimen experienced disease control (1 partial response, 7 stable disease) for a median of 18 months (range 6–72 months).
Conclusions
These results support our previous finding that a subset of pulmonary carcinoid tumors are responsive to chemotherapy
Association Between Interstitial Lung Abnormalities and All-Cause Mortality.
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This article is open access.Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated.To investigate whether interstitial lung abnormalities are associated with increased mortality.Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006).Interstitial lung abnormality status as determined by chest CT evaluation.All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort.Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis.In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.National Institutes of Health (NIH)
T32 HL007633
Icelandic Research Fund
141513-051
Landspitali Scientific Fund
A-2015-030
National Cancer Institute grant
1K23CA157631
NIH
K08 HL097029
R01 HL113264
R21 HL119902
K25 HL104085
R01 HL116931
R01 HL116473
K01 HL118714
R01 HL089897
R01 HL089856
N01-AG-1-2100
HHSN27120120022C
P01 HL105339
P01 HL114501
R01 HL107246
R01 HL122464
R01 HL111024
National Heart, Lung, and Blood Institute's Framingham Heart Study contract
N01-HC-2519.5
GlaxoSmithKline
NCT00292552
5C0104960
National Institute on Aging (NIA) grant
27120120022C
NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association)
Althingi (the Icelandic Parliament)
NIA
27120120022
A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response
Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers1–4. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy1,3. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors5–9, has not been fully explored. Here we use genetically engineered mouse models to conduct a ‘co-clinical’ trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244)10 increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors6,9,11,12, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies
Molecular imprinting science and technology: a survey of the literature for the years 2004-2011
Perinodular Radiomic Features to Assess Nodule Microenvironment: Does It Help to Distinguish Malignant versus Benign Lung Nodules?
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