Accelerated large volume irradiation with dynamic Jaw/Dynamic Couch Helical Tomotherapy

BACKGROUND: Helical Tomotherapy (HT) has unique capacities for the radiotherapy of large and complicated target volumes. Next generation Dynamic Jaw/Dynamic Couch HT delivery promises faster treatments and reduced exposure of organs at risk due to a reduced dose penumbra. METHODS: Three challenging clinical situations were chosen for comparison between Regular HT delivery with a field width of 2.5 cm (Reg 2.5) and 5.0 cm (Reg 5.0) and DJDC delivery with a maximum field width of 5.0 cm (DJDC 5.0): Hemithoracic Irradiation, Whole Abdominal Irradiation (WAI) and Total Marrow Irradiation (TMI). For each setting, five CT data sets were chosen, and target coverage, conformity, integral dose, dose exposure of organs at risk (OAR) and treatment time were calculated. RESULTS: Both Reg 5.0 and DJDC 5.0 achieved a substantial reduction in treatment time while maintaining similar dose coverage. Treatment time could be reduced from 10:57 min to 3:42 min / 5:10 min (Reg 5.0 / DJDC 5.0) for Hemithoracic Irradiation, from 18:03 min to 8:02 min / 8:03 min for WAI and to 18:25 min / 18:03 min for TMI. In Hemithoracic Irradiation, OAR exposure was identical in all modalities. For WAI, Reg 2.5 resulted in lower exposure of liver and bone. DJDC plans showed a small but significant increase of ∼ 1 Gy to the kidneys, the parotid glans and the thyroid gland. While Reg 5.0 and DJDC were identical in terms of OAR exposure, integral dose was substantially lower with DJDC, caused by a smaller dose penumbra. CONCLUSIONS: Although not clinically available yet, next generation DJDC HT technique is efficient in improving the treatment time while maintaining comparable plan quality

Prevention of bone growth defects, increased bone resorption and marrow adiposity with folinic acid in rats receiving long-term methotrexate

The underlying pathophysiology for bone growth defects in paediatric cancer patients receiving high dose methotrexate chemotherapy remains unclear and currently there are no standardized preventative treatments for patients and survivors. Using a model in young rats, we investigated damaging effects of long-term treatment with methotrexate on growth plate and metaphyseal bone, and the potential protective effects of antidote folinic acid. This study demonstrated that chronic folinic acid supplementation can prevent methotrexate-induced chondrocyte apoptosis and preserve chondrocyte columnar arrangement and number in the growth plate. In the metaphysis, folinic acid supplementation can preserve primary spongiosa heights and secondary spongiosa trabecular volume by preventing osteoblasts from undergoing apoptosis and suppressing methotrexate-induced marrow adiposity and osteoclast formation. Systemically, plasma of folinic acid supplemented rats, in comparison to plasma from rats treated with MTX alone, contained a significantly lower level of IL-1b and suppressed osteoclast formation in vitro in normal bone marrow cells. The importance of IL-1b in supporting plasma-induced osteoclast formation was confirmed as the presence of an anti-IL-1b neutralizing antibody attenuated the ability of the plasma (from MTX-treated rats) in inducing osteoclast formation. Findings from this study suggest that folinic acid supplementation during chronic methotrexate treatment can alleviate growth plate and metaphyseal damages and therefore may be potentially useful in paediatric patients who are at risk of skeletal growth suppression due to chronic methotrexate chemotherapy.Chia-Ming Fan, Bruce K. Foster, Susanta K. Hui and Cory J. Xia

Treatment planning of total marrow irradiation with intensity-modulated spot-scanning proton therapy

PurposeThe goal of this study is to investigate treatment planning of total marrow irradiation (TMI) using intensity-modulated spot-scanning proton therapy (IMPT). The dosimetric parameters of the intensity-modulated proton plans were evaluated and compared with the corresponding TMI plans generated with volumetric modulated arc therapy (VMAT) using photon beams.MethodsIntensity-modulated proton plans for TMI were created using the Monte Carlo dose-calculation algorithm in the Raystation 11A treatment planning system with spot-scanning proton beams from the MEVION S250i Hyperscan system. Treatment plans were generated with four isocenters placed along the longitudinal direction, each with a set of five beams for a total of 20 beams. VMAT-TMI plans were generated with the Eclipse-V15 analytical anisotropic algorithm (AAA) using a Varian Trilogy machine. Three planning target volumes (PTVs) for the bones, ribs, and spleen were covered by 12 Gy. The dose conformity index, D80, D50, and D10, for PTVs and organs at risk (OARs) for the IMPT plans were quantified and compared with the corresponding VMAT plans.ResultsThe mean dose for most of the OARs was reduced substantially (5% and more) in the IMPT plans for TMI in comparison with VMAT plans except for the esophagus and thyroid, which experienced an increase in dose. This dose reduction is due to the fast dose falloff of the distal Bragg peak in the proton plans. The conformity index was found to be similar (0.78 vs 0.75) for the photon and proton plans. IMPT plans provided superior superficial dose coverage for the skull and ribs in comparison with VMAT because of increased entrance dose deposition by the proton beams.ConclusionTreatment plans for TMI generated with IMPT were superior to VMAT plans mainly due to a large reduction in the OAR dose. Although the current IMPT-TMI technique is not clinically practical due to the long overall treatment time, this study presents an enticing alternative to conventional TMI with photons by providing superior dose coverage of the targets, increased sparing of the OARs, and enhanced radiobiological effects associated with proton therapy

Feasibility of a Novel Sparse Orthogonal Collimator–Based Preclinical Total Marrow Irradiation for Enhanced Dosimetric Conformality

Total marrow irradiation (TMI) has significantly improved radiation conditioning for hematopoietic cell transplantation in hematologic diseases by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. Recently, preclinical three-dimensional image–guided TMI has been developed to enhance mechanistic understanding of the role of TMI and to support the development of experimental therapeutics. However, a dosimetric comparison between preclinical and clinical TMI reveals that the preclinical TMI treatment lacks the ability to reduce the dose to some of the vital organs that are very close to the skeletal system and thus limits the ability to evaluate radiobiological relevance. To overcome this limit, we introduce a novel Sparse Orthogonal Collimator (SOC)–based TMI and evaluate its ability to enhance dosimetric conformality. The SOC-TMI–based dose modulation technique significantly improves TMI treatment planning by reducing radiation exposures to critical organs that are close to the skeletal system that leads to reducing the gap between clinical and preclinical TMI

Fast, simple, and informative patient-specific dose verification method for intensity modulated total marrow irradiation with helical tomotherapy

BACKGROUND: Patient-specific dose verification for treatment planning in helical tomotherapy is routinely performed using a homogeneous virtual water cylindrical phantom of 30 cm diameter and 18 cm length (Cheese phantom). Because of this small length, treatment with total marrow irradiation (TMI) requires multiple deliveries of the dose verification procedures to cover a wide range of the target volumes, which significantly prolongs the dose verification process. We propose a fast, simple, and informative patient-specific dose verification method which reduce dose verification time for TMI with helical tomotherapy. METHODS: We constructed a two-step solid water slab phantom (length 110 cm, height 8 cm, and two-step width of 30 cm and 15 cm), termed the Whole Body Phantom (WB phantom). Three ionization chambers and three EDR-2 films can be inserted to cover extended field TMI treatment delivery. Three TMI treatment plans were conducted with a TomoTherapy HiArt Planning Station and verified using the WB phantom with ion chambers and films. Three regions simulating the head and neck, thorax, and pelvis were covered in a single treatment delivery. The results were compared to those with the cheese phantom supplied by Accuray, Inc. following three treatment deliveries to cover the body from head to pelvis. RESULTS: Use of the WB phantom provided point doses or dose distributions from head and neck to femur in a single treatment delivery of TMI. Patient-specific dose verification with the WB phantom was 62% faster than with the cheese phantom. The average pass rate in gamma analysis with the criteria of a 3-mm distance-to-agreement and 3% dose differences was 94% ± 2% for the three TMI treatment plans. The differences in pass rates between the WB and cheese phantoms at the upper thorax to abdomen regions were within 2%. The calculated dose agreed with the measured dose within 3% for all points in all five cases in both the WB and cheese phantoms. CONCLUSIONS: Our dose verification method with the WB phantom provides simple and rapid quality assurance without limiting dose verification information in total marrow irradiation with helical tomotherapy

The development of a mechano-biological assessment of leukemia cells using optical tweezers

Patients with B-ALL (Ph +ve) acute lymphoblastic leukemia are at high risk of relapse and mortality. We seek to establish a mechano-biological testing technique to assess biophysical properties of cell motility, potentiating the ability to distinguish between high and low risk leukemia populations and behaviors. Two experiments were performed to test the mechano-biological behavior of B-ALL using the ThorLabs modular optical tweezers and a microfluid chemotaxis chamber. The first experiment measured the relative mechanical energy carried by a cell in the optical trap, which was performed on B-ALL in control conditions and under SDF1 chemotaxis. The relative mechanical energy was found through an extension of the back-focal-plane calibration method for optical tweezers, and assumed that increased cellular activity manifests as random movements. There was no discernable difference in the relative mechanical energies between the control B-ALL, B-ALL under SDF1 chemotaxis, and B-ALL in the presence of mesenchymal stem cells. The second experiment quantified the real-time migrational force of B-ALL under SDF1 chemotaxis. This was found through prior calibration of the optical tweezers through determination of the terms κ and β. Of the viable measurements, 3 of 8 cells exhibited a significant force towards the SDF1 gradient. Further experimentation is necessary to normalize the experimental set-up conditions, and increase the number of viable measurements during cell migration

Feasibility of intrafraction whole-body motion tracking for total marrow irradiation

With image-guided tomotherapy, highly targeted total marrow irradiation (TMI) has become a feasible alternative to conventional total body irradiation. The uncertainties in patient localization and intrafraction motion of the whole body during hour-long TMI treatment may pose a risk to the safety and accuracy of targeted radiation treatment. The feasibility of near-infrared markers and optical tracking system (OTS) is accessed along with a megavoltage scanning system of tomotherapy. Three near-infrared markers placed on the face of a rando phantom are used to evaluate the capability of OTS in measuring changes in the markers’ positions as the rando is moved in the translational direction. The OTS is also employed to determine breathing motion related changes in the position of 16 markers placed on the chest surface of human volunteers. The maximum uncertainty in locating marker position with the OTS is 1.5 mm. In the case of normal and deep breathing motion, the maximum marker position change is observed in anterior–posterior direction with the respective values of 4 and 12 mm. The OTS is able to measure surface changes due to breathing motion. The OTS may be optimized to monitor whole body motion during TMI to increase the accuracy of treatment delivery and reduce the radiation dose to the lungs