Carfilzomib, bendamustine, and dexamethasone in patients with advanced multiple myeloma: The EMN09 phase 1/2 study of the European Myeloma Network

Background: Combined therapy with carfilzomib, bendamustine, and dexamethasone was evaluated in this multicenter phase 1/2 trial conducted within the European Myeloma Network (EMN09 trial). Methods: Sixty-three patients with relapsed/refractory multiple myeloma who had received 652 lines of prior therapy were included. The phase 1 portion of the study determined the maximum tolerated dose of carfilzomib with bendamustine set at 70 mg/m2 on days 1 and 8. After 8 cycles, responding patients received maintenance therapy with carfilzomib and dexamethasone until progression. Results: On the basis of the phase 1 results, the recommended phase 2 dose for carfilzomib was 27 mg/m2 twice weekly in weeks 1, 2, and 3. Fifty-two percent of patients achieved a partial response or better, and 32% reached a very good partial response or better. The clinical benefit rate was 93%. After a median follow-up of 21.9 months, the median progression-free survival was 11.6 months, and the median overall survival was 30.4 months. The reported grade 653 hematologic adverse events (AEs) were lymphopenia (29%), neutropenia (25%), and thrombocytopenia (22%). The main nonhematologic grade 653 AEs were pneumonia, thromboembolic events (10%), cardiac AEs (8%), and hypertension (2%). Conclusions: In heavily pretreated patients who have relapsed/refractory multiple myeloma, combined carfilzomib, bendamustine, and dexamethasone is an effective treatment option administered in the outpatient setting. Infection prophylaxis and attention to patients with cardiovascular predisposition are required

Flattening filter-free accelerators: a report from the AAPM Therapy Emerging Technology Assessment Work Group.

This report describes the current state of flattening filter-free (FFF) radiotherapy beams implemented on conventional linear accelerators, and is aimed primarily at practicing medical physicists. The Therapy Emerging Technology Assessment Work Group of the American Association of Physicists in Medicine (AAPM) formed a writing group to assess FFF technology. The published literature on FFF technology was reviewed, along with technical specifications provided by vendors. Based on this information, supplemented by the clinical experience of the group members, consensus guidelines and recommendations for implementation of FFF technology were developed. Areas in need of further investigation were identified. Removing the flattening filter increases beam intensity, especially near the central axis. Increased intensity reduces treatment time, especially for high-dose stereotactic radiotherapy/radiosurgery (SRT/SRS). Furthermore, removing the flattening filter reduces out-of-field dose and improves beam modeling accuracy. FFF beams are advantageous for small field (e.g., SRS) treatments and are appropriate for intensity-modulated radiotherapy (IMRT). For conventional 3D radiotherapy of large targets, FFF beams may be disadvantageous compared to flattened beams because of the heterogeneity of FFF beam across the target (unless modulation is employed). For any application, the nonflat beam characteristics and substantially higher dose rates require consideration during the commissioning and quality assurance processes relative to flattened beams, and the appropriate clinical use of the technology needs to be identified. Consideration also needs to be given to these unique characteristics when undertaking facility planning. Several areas still warrant further research and development. Recommendations pertinent to FFF technology, including acceptance testing, commissioning, quality assurance, radiation safety, and facility planning, are presented. Examples of clinical applications are provided. Several of the areas in which future research and development are needed are also indicated

Variations in photon energy spectra of a 6 MV beam and their impact on TLD response

Purpose: Measurement of the absorbed dose from radiotherapy beams is an essential component of providing safe and reproducible treatment. For an energy-dependent dosimeter such as thermoluminescent dosimeters (TLDs), it is generally assumed that the energy spectrum is constant throughout the treatment field and is unperturbed by field size, depth, field modulation, or heterogeneities. However, this does not reflect reality and introduces error into clinical dose measurements. The purpose of this study was to evaluate the variability in the energy spectrum of a Varian 6 MV beam and to evaluate the impact of these variations in photon energy spectra on the response of a common energy-dependent dosimeter, TLD