Reducing Radiation Dose at Chest CT: Comparison Among Model-based Type Iterative Reconstruction, Hybrid Iterative Reconstruction, and Filtered Back Projection.

The study aimed to evaluate the performances of two iterative reconstruction (IR) algorithms and of filtered back projection (FBP) when using reduced-dose chest computed tomography (RDCT) compared to standard-of-care CT. An institutional review board approval was obtained. Thirty-six patients with hematologic malignancies referred for a control chest CT of a known lung disease were prospectively enrolled. Patients underwent standard-of-care scan reconstructed with hybrid IR, followed by an RDCT reconstructed with FBP, hybrid IR, and iterative model reconstruction. Objective and subjective quality measurements, lesion detectability, and evolution assessment on RDCT were recorded. For RDCT, the CTDIvol (volumetric computed tomography dose index) was 0.43 mGy⋅cm for all patients, and the median [interquartile range] effective dose was 0.22 mSv [0.22-0.24]; corresponding measurements for standard-of-care scan were 3.4 mGy [3.1-3.9] and 1.8 mSv [1.6-2.0]. Noise significantly decreased from FBP to hybrid IR and from hybrid IR to iterative model reconstruction on RDCT, whereas lesion conspicuity and diagnostic confidence increased. Accurate evolution assessment was obtained in all cases with IR. Emphysema identification was higher with iterative model reconstruction. Although iterative model reconstruction offered better diagnostic confidence and emphysema detection, both IR algorithms allowed an accurate evolution assessment with an effective dose of 0.22 mSv

Sustained response to salvage therapy for dabrafenib-resistant metastatic Langerhans cell sarcoma

International audienceLangerhans cell sarcoma (LCS) is a rare high-grade malignancy of Langerhans cells involving the lymphatic system and extranodal sites [1.]. Patients with multiorgan involvement have a poor prognosis and a high mortality rate despite treatment with several chemotherapeutic regimens [1.]. LCS tumor cells may harbor the BRAFV600E mutation [2.], which suggests that these patients may benefit from BRAF inhibitors (BRAFi). We recently reported the marked improvement of a 58-year-old male patient with metastatic BRAFV600E-mutated LCS following treatment with the BRAFi dabrafenib, but unfortunately the disease recurred after 6 months of treatment [3.]. Here, we describe the subsequent impressive and sustained response achieved using a combination of the BRAFi vemurafenib and the MAPK kinase inhibitor (MEKi) cobimetinib.The general condition of this patient had deteriorated at the time of LCS recurrence. The patient had an Eastern Cooperative Oncology Group (ECOG) performance status of 4, a 39°C fever and intense biological inflammatory syndrome (CRP: 328 mg/l). At this time, lung computed tomography (CT) showed progression of LCS as a large left mediastinal and pulmonary tumor with lymphangitic carcinomatosis and concurrent left axillary adenopathy (Figure 1A). We obtained informed consent before initiating vemurafenib (960 mg twice daily) and cobimetinib (60 mg once daily for 21 days per 28-day cycle). The patient dramatically improved and became afebrile on day 3 of treatment. After 3 months, the patient's ECOG performance status was 1. The mediastinal tumor completely resolved, and the pulmonary and axillary lesions decreased by 80% compared with baseline (Figure 1A). The patient had a partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. After 12 months of treatment, he was stable and maintained a radiological response. There was minimal fluorodeoxyglucose (18-FDG) uptake, as observed by positron emission tomography (PET)-CT, in the pulmonary and axillary lesions, confirming the persistent control of the disease (Figure 1A). The treatment was well tolerated, with the exception of a cutaneous rash that spontaneously resolved. The plasma concentrations of cobimetinib and vemurafenib were measured monthly at steady state (day 15 of each cycle) and reached the median values (range) of 72.7 ng/ml (47–95.4) and 39.8 µg/ml (32.1–49.8), respectively, which are consistent with the results of previous pharmacokinetic studies. The BRAFV600E mutation levels were monitored in the patient's plasma before and after treatment using the Enhanced-Ice-Cold-PCR technique, as previously described [4.]. The BRAFV600E mutation level (percent mutant allele fraction) decreased from 2.3% at the time of LCS recurrence to values below the sensitivity threshold (0.5%) at day 60, which was maintained throughout treatment (Figure 1B)