Meeting report : 1st international functional metagenomics workshop May 7–8, 2012, St. Jacobs, Ontario, Canada

This report summarizes the events of the 1st International Functional Metagenomics Workshop. The workshop was held on May 7 and 8 in St. Jacobs, Ontario, Canada and was focused on building a core international functional metagenomics community, exploring strategic research areas, and identifying opportunities for future collaboration and funding. The workshop was initiated by researchers at the University of Waterloo with support from the Ontario Genomics Institute (OGI), Natural Sciences and Engineering Research Council of Canada (NSERC) and the University of Waterloo

Adaptive Radiation Therapy (ART) Strategies and Technical Considerations: A State of the ART Review From NRG Oncology

The integration of adaptive radiation therapy (ART), or modifying the treatment plan during the treatment course, is becoming more widely available in clinical practice. ART offers strong potential for minimizing treatment-related toxicity while escalating or de-escalating target doses based on the dose to organs at risk. Yet, ART workflows add complexity into the radiation therapy planning and delivery process that may introduce additional uncertainties. This work sought to review presently available ART workflows and technological considerations such as image quality, deformable image registration, and dose accumulation. Quality assurance considerations for ART components and minimum recommendations are described. Personnel and workflow efficiency recommendations are provided, as is a summary of currently available clinical evidence supporting the implementation of ART. Finally, to guide future clinical trial protocols, an example ART physician directive and a physics template following standard NRG Oncology protocol is provided

Evaluating organ delineation, dose calculation and daily localization in an open-MRI simulation workflow for prostate cancer patients

BACKGROUND: This study describes initial testing and evaluation of a vertical-field open Magnetic Resonance Imaging (MRI) scanner for the purpose of simulation in radiation therapy for prostate cancer. We have evaluated the clinical workflow of using open MRI as a sole modality for simulation and planning. Relevant results related to MRI alignment (vs. CT) reference dataset with Cone-Beam CT (CBCT) for daily localization are presented. METHODS: Ten patients participated in an IRB approved study utilizing MRI along with CT simulation with the intent of evaluating the MRI-simulation process. Differences in prostate gland volume, seminal vesicles, and penile bulb were assessed with MRI and compared to CT. To evaluate dose calculation accuracy, bulk-density-assignments were mapped onto respective MRI datasets and treated IMRT plans were re-calculated. For image localization purposes, 400 CBCTs were re-evaluated with MRI as the reference dataset and daily shifts compared against CBCT-to-CT registration. Planning margins based on MRI/CBCT shifts were computed using the van Herk formalism. RESULTS: Significant organ contour differences were noted between MRI and CT. Prostate volumes were on average 39.7% (p = 0.002) larger on CT than MRI. No significant difference was found in seminal vesicle volumes (p = 0.454). Penile bulb volumes were 61.1% higher on CT, without statistical significance (p = 0.074). MRI-based dose calculations with assigned bulk densities produced agreement within 1% with heterogeneity corrected CT calculations. The differences in shift positions for the cohort between CBCT-to-CT registration and CBCT-to-MRI registration are −0.15 ± 0.25 cm (anterior-posterior), 0.05 ± 0.19 cm (superior-inferior), and −0.01 ± 0.14 cm (left-right). CONCLUSIONS: This study confirms the potential of using an open-field MRI scanner as primary imaging modality for prostate cancer treatment planning simulation, dose calculations and daily image localization

Spezifische Immuntherapie mit rekombinanter Birkenpollenallergen-rBet v1-FV ist klinisch wirksam

Einleitung: Allergenpräparate aus Pollenextrakten sowie chemisch modifizierte Allergoide werden in der allergenspezifischen Immuntherapie erfolgreich eingesetzt. Rekombinante Birkenpollenallergene bieten viele potentielle Vorteile im Hinblick auf pharmazeutische Qualität, Standardisierung und Dosierung.Methoden: In einer randomisierten kontrollierten Phase II-Studie mit Rhinitispatienten +/- Asthma auf Birkenallergen wurde das rekombinante Allergenderivat rBet v1-FV mit einem eingeführten Birkenpollen-Präparat verglichen. 51 Patienten (24 rBet v1-FV und 27 Kontrollen) begannen die Therapie mit subkutanen Injektionen steigender Dosen, denen Erhaltungsdosen bis zum Beginn der Birkenpollensaison 2004 folgten.Ergebnisse: Nach einer präsaisonalen Behandlung wurde ein mittlerer (täglicher) Symptom-Medikation-Score (SMS) von 5.90 für rBet v1-FV gegenüber 12.48 für Kontrollen festgestellt, der einem um 53% niedrigeren SMS in der Bet v1-FV-Gruppe entsprach (n=22/17, rBet v1-FV/Kontrolle). Die Allergentoleranz im nasalen Provokationstest sowie das Patientenurteil nach der visuellen Analogskala waren in beiden Gruppen vergleichbar, wogegen ein 25- gegenüber 11facher IgG1- (45- gegenüber 12facher IgG4-Anstieg) für das rekombinante bzw. native Allergenpräparat zu beobachten war. Art und Schweregrad unerwünschter Ereignisse waren unter rBet v1-FV mit denen beim nativen Pollenpräparat vergleichbar.Schlussfolgerungen: Das rekombinante Birkenpollenallergen-Präparat rBet v1-FV hat sich bei Birkenpollen-Allergie mit oder ohne Asthma (GINA I oder II) als gut verträglich und klinisch wirksam erwiesen. Dies ist die erste klinische Anwendung des rekombinanten rBet v1-FV sowie der erste Vergleich mit einem eingeführten SIT-Präparat.Unterstützt durch ALLERGOPHARM

Precision experiments with rare isotopes with LEBIT at MSU

The Low-Energy Beam and Ion Trap facility LEBIT at the NSCL is in the final phase of commissioning. Gas stopping of fast fragment beams and modern ion manipulation techniques are used to provide beams for high-precision mass measurements and other experiments. The status of the facility and the result of first test mass measurements on stable krypton isotopes are presented

Evaluating organ delineation, dose calculation and daily localization in an open-MRI simulation workflow for prostate cancer patients

BACKGROUND: This study describes initial testing and evaluation of a vertical-field open Magnetic Resonance Imaging (MRI) scanner for the purpose of simulation in radiation therapy for prostate cancer. We have evaluated the clinical workflow of using open MRI as a sole modality for simulation and planning. Relevant results related to MRI alignment (vs. CT) reference dataset with Cone-Beam CT (CBCT) for daily localization are presented. METHODS: Ten patients participated in an IRB approved study utilizing MRI along with CT simulation with the intent of evaluating the MRI-simulation process. Differences in prostate gland volume, seminal vesicles, and penile bulb were assessed with MRI and compared to CT. To evaluate dose calculation accuracy, bulk-density-assignments were mapped onto respective MRI datasets and treated IMRT plans were re-calculated. For image localization purposes, 400 CBCTs were re-evaluated with MRI as the reference dataset and daily shifts compared against CBCT-to-CT registration. Planning margins based on MRI/CBCT shifts were computed using the van Herk formalism. RESULTS: Significant organ contour differences were noted between MRI and CT. Prostate volumes were on average 39.7% (p = 0.002) larger on CT than MRI. No significant difference was found in seminal vesicle volumes (p = 0.454). Penile bulb volumes were 61.1% higher on CT, without statistical significance (p = 0.074). MRI-based dose calculations with assigned bulk densities produced agreement within 1% with heterogeneity corrected CT calculations. The differences in shift positions for the cohort between CBCT-to-CT registration and CBCT-to-MRI registration are -0.15 ± 0.25 cm (anterior-posterior), 0.05 ± 0.19 cm (superior-inferior), and -0.01 ± 0.14 cm (left-right). CONCLUSIONS: This study confirms the potential of using an open-field MRI scanner as primary imaging modality for prostate cancer treatment planning simulation, dose calculations and daily image localization

MRI-guided Radiotherapy (MRgRT) for treatment of Oligometastases: Review of clinical applications and challenges

PURPOSE: Early clinical results on the application of magnetic resonance imaging (MRI) coupled with a linear accelerator to deliver MR-guided radiation therapy (MRgRT) have demonstrated feasibility for safe delivery of stereotactic body radiotherapy (SBRT) in treatment of oligometastatic disease. Here we set out to review the clinical evidence and challenges associated with MRgRT in this setting. METHODS AND MATERIALS: We performed a systematic review of the literature pertaining to clinical experiences and trials on the use of MRgRT primarily for the treatment of oligometastatic cancers. We reviewed the opportunities and challenges associated with the use of MRgRT. RESULTS: Benefits of MRgRT pertaining to superior soft-tissue contrast, real-time imaging and gating, and online adaptive radiotherapy facilitate safe and effective dose escalation to oligometastatic tumors while simultaneously sparing surrounding healthy tissues. Challenges concerning further need for clinical evidence and technical considerations related to planning, delivery, quality assurance (QA) of hypofractionated doses, and safety in the MRI environment must be considered. CONCLUSIONS: The promising early indications of safety and effectiveness of MRgRT for SBRT-based treatment of oligometastatic disease in multiple treatment locations should lead to further clinical evidence to demonstrate the benefit of this technology

Long-Term Multi-Institutional Outcomes of 5-Fraction Ablative Stereotactic MR-Guided Adaptive Radiation Therapy (SMART) for Inoperable Pancreas Cancer With Median Prescribed Biologically Effective Dose of 100 Gy10

Purpose/Objective(s): Randomized trials have shown improved local control (LC) but no overall survival (OS) benefit with the addition of non-ablative radiation therapy (RT) dose compared to chemotherapy (CT) alone for pancreas cancer (PCa). Emerging data suggest that dose-escalated RT may improve LC and OS. A few studies suggest that stereotactic magnetic resonance-guided adaptive RT (SMART) can facilitate the safe delivery of ablative dose for inoperable PCa, although long-term outcomes are not well understood. Materials/Methods: Inoperable PCa patients who received SMART were identified from the RSSearch Registry. Patients with \u3c 3 months (mo.) follow-up after SMART were excluded. LC, progression free survival (PFS), and OS were estimated using the Kaplan-Meier method. LC was evaluated according to RECIST 1.1 criteria. Acute toxicity was considered within 90 days of SMART and evaluated by CTCAE v4 criteria. Results: A total of 148 PCa patients were treated on a 0.35T MR LINAC across 3 institutions between 2018-2020. Median age was 68 years (range 47-91), and 73.6% had ECOG 0-1 performance status. Patients had locally advanced (57.4%), borderline resectable (29.1%), or medically inoperable (13.5%) disease. Median CA19-9 at diagnosis was 202.1 U/mL (range 0.9-21,281). Induction CT was delivered to 89.2% for a median 3.9 mo (range 0.2-11.3); FOLFIRINOX (52.7%) or gemcitabine/nab-paclitaxel (23.4%) were common. Median prescribed RT dose was 50 Gy (range 40-50) in 5 fractions, mostly in consecutive days (96.6%) and in breath hold (95.3%). Median biologically effective dose (BED10) was 100 Gy10. All patients were treated with real-time tissue tracking and automated beam gating without fiducial markers. An elective target volume was rarely used (25%). Pancreaticoduodenectomy was performed in 23% at a median 46 days (range 34-304) after SMART. Median follow-up was 16 mo. from diagnosis for all patients (range, 4-39). Median, 1-year, and 2-year LC was not reached (NR), 94.6%, and 83%, respectively. Median, 1-year, and 2-year PFS was 18 mo., 72%, and 35.9%, respectively. Median, 1-year, and 2-year OS was 26 mo., 82%, and 52.7%, respectively. Acute and late grade 3 toxicity possibly related to SMART occurred in 4.1% and 12.8%, respectively. There was no reported grade 4+ toxicity. Conclusion: To our knowledge, this is the largest reported analysis of 5-fraction SMART for inoperable PCa. These data add to the evidence that ablative radiation dose may improve long-term outcomes including OS. Prospective evaluation of this novel approach is warranted with attention directed at optimizing patient selection, understanding the clinical significance of cumulative dose delivered across all adapted fractions, and assessing treatment response after the delivery of ablative dose

Benchmarking of Low-Field MR-Linacs in a Multi-Institutional International Consortium

Purpose: Recently, MR-linacs have been integrated into clinical practice, introducing new needs for QA and baseline machine characterization. This work summarizes a multi-institutional evaluation 12 low-field MR-linacs with the overarching goal of benchmarking machine performance. Methods: Acceptance and commissioning data were analyzed for 12 0.35 T ViewRay MRIdian linacs equipped with double-focused MLCs (4 mm aperture resolution). MRI-radiation isocenter accuracy was assessed. Couch transmission was measured at various beam angle incidences. Dosimetric evaluation included 6XFFF photon beam spot size, profiles, PDD curves, chamber-corrected Monte-Carlo derived relative photon OFs (0.83-25.6 cm2 field sizes), temporal output factor stability, and MLC transmission/leakage. End-to-end testing and IMRT performance were evaluated. MRI benchmarking included spatial integrity, magnetic field homogeneity (MFH) using spectral peak analysis (5-12 gantry angles), and image quality evaluation via ACR/NEMA standards. Clinical integration including QA timelines, staffing, and equipment were summarized. Results: MRI/laser/radiation isocenter coincidence was ≤0.8 mm for all MR-linacs. Couch transmission ranged from 13% to 17% (180° and 140°, respectively) requiring inclusion in treatment planning. Excellent agreement in PDD(10)x was observed (64.1 ± 0.4%) with spot sizes of 0.15 ± 0.03 mm. The largest discrepancy in corrected OFs was 0.72 ± 0.03 (0.83 cm2 field size) while all other OFs were in close agreement. Average output values within 2-18 months of initial calibration were \u3c1% of nominal; four institutions adjusted output at ∼90 days. On average, MLC transmission and leakage were \u3c0.3% and all IMRT plans were within 99% agreement of expected (3%/3 mm). MRI ACR and vendor-specified limits were met for all image quality metrics. Gantryangle dependence of MFH was observed (2.93 ± 1.82 ppm) with 3/12 institutions exceeding 5 ppm at a subset of angles, warranting a dynamic gantry angle-dependent shim. Conclusion: Overall, excellent agreement in multiinstitutional commissioning data was observed, providing important comparison data to others embarking on MR-linac commissioning