Total marrow and lymphoid irradiation with helical tomotherapy: A practical implementation report

2020 ◽  
Author(s):  
Srinivas Chilukuri ◽  
Sham Sundar ◽  
Rajesh Thiyagarajan ◽  
Jose Easow ◽  
Mayur Sawant ◽  
...  
Keyword(s):  
Helical Tomotherapy ◽  
Organs At Risk ◽  
Conditioning Regimen ◽  
Ct Scanning ◽  
Whole Body ◽  
Patient Specific ◽  
Practical Implementation ◽  
Allogenic Bone ◽  
Megavoltage Ct

Abstract Objective To standardize the technique and resources for total marrow and lymphoid irradiation (TMLI) as part of the conditioning regimen before allogenic bone marrow transplantation (ABMT) using helical tomotherapy.Methods We used this technique in our first 5 patients requiring TMLI. Patients were immobilized using a mask and a whole-body vacuum cushion. CT scanning was performed in head first supine (HFS) and feet first supine (FFS) orientations with an overlap at mid-thigh. Target consisted of the entire skeleton, spleen, sanctuary sites and major lymphatics whereas lungs, kidneys, aero-digestive tract, bowel, parotids, heart and liver were defined as organs at risk (OAR). Treatment was performed in two parts based on 2 different plans generated in HFS and FFS orientations with an overlap at the mid thigh. Patients along with the immobilization device were manually rotated by 180° to change the orientation after the delivery of HFS plan. The dose at the junction was contributed by a complementary dose gradient from each of the plans. Plan was to deliver 95% of 12Gy to 98% of CTV with dose heterogeneity < 10% and pre-specified OAR doe constraints. Megavoltage-CT was used for position verification before each fraction. Patient specific quality assurance and an in-vivo film dosimetry to verify junction dose were performed in all patients.Results Treatment was delivered in two daily fractions of 2Gy each for 3 days with at least 8-hours gap between each fraction. The target coverage goals were met in all the patients. The average person-hours per patient were 16.5, 21.5 and 25.75 for radiation oncologist, radiation therapist and medical physicist respectively. Average in-room time per patient was 9.25 hours with an average beam-on time of 3.32 hours for all the six fractions. Conclusion This report comprehensively describes technique and resource requirements for TMLI and would serve as a practical guide for departments keen to start this service. Despite being time and labor intensive, it can be implemented safely and robustly. We will be using this methodology in a prospective phase II trial to study safety and feasibility of dose escalated TMLI as part of conditioning regimen before ABMT.

Design, Fabrication, and Accuracy of a Novel Noncovering Lock-Mechanism Bilateral Patient-Specific Drill Guide Template for Nondeformed and Deformed Thoracic Spines

2021 ◽  
pp. 155633162199633
Author(s):  
Mehran Ashouri-Sanjani ◽  
Shima Mohammadi-Moghadam ◽  
Parisa Azimi ◽  
Navid Arjmand
Keyword(s):  
Thoracic Spine ◽  
Sagittal Plane ◽  
Ct Scanning ◽  
Entry Point ◽  
In Vivo Studies ◽  
Patient Specific ◽  
Plane Angle ◽  
Severe Scoliosis ◽  
3D Printed

Background: Pedicle screw (PS) placement has been widely used in fusion surgeries on the thoracic spine. Achieving cost-effective yet accurate placements through nonradiation techniques remains challenging. Questions/Purposes: Novel noncovering lock-mechanism bilateral vertebra-specific drill guides for PS placement were designed/fabricated, and their accuracy for both nondeformed and deformed thoracic spines was tested. Methods: One nondeformed and 1 severe scoliosis human thoracic spine underwent computed tomographic (CT) scanning, and 2 identical proportions of each were 3-dimensional (3D) printed. Pedicle-specific optimal (no perforation) drilling trajectories were determined on the CT images based on the entry point/orientation/diameter/length of each PS. Vertebra-specific templates were designed and 3D printed, assuring minimal yet firm contacts with the vertebrae through a noncovering lock mechanism. One model of each patient was drilled using the freehand and one using the template guides (96 pedicle drillings). Postoperative CT scans from the models with the inserted PSs were obtained and superimposed on the preoperative planned models to evaluate deviations of the PSs. Results: All templates fitted their corresponding vertebra during the simulated operations. As compared with the freehand approach, PS placement deviations from their preplanned positions were significantly reduced: for the nonscoliosis model, from 2.4 to 0.9 mm for the entry point, 5.0° to 3.3° for the transverse plane angle, 7.1° to 2.2° for the sagittal plane angle, and 8.5° to 4.1° for the 3D angle, improving the success rate from 71.7% to 93.5%. Conclusions: These guides are valuable, as the accurate PS trajectory could be customized preoperatively to match the patients’ unique anatomy. In vivo studies will be required to validate this approach.

Linac Based Total Marrow Irradiation and Myeloablative Chemotherapy In Allogeneic Stem Cell Transplantation for High Risk Patients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4526-4526
Author(s):  
Pritesh R. Patel ◽  
Bulent Aydogan ◽  
Damiano Rondelli
Keyword(s):  
Linear Accelerator ◽  
Treatment Time ◽  
Conflicts Of Interest ◽  
Organs At Risk ◽  
Chronic Gvhd ◽  
Ct Scanning ◽  
Test Dose ◽  
Target Volume ◽  
Whole Body ◽  
Total Marrow Irradiation

Abstract Abstract 4526 Intensity modulated total marrow irradiation (IM-TMI) represents an innovative technique to irradiate the bone marrow in hematologic malignancies. IM-TMI has been performed previously using tomotherapy in combination with a reduced intensity preparative regimen. Here we report 2 cases where IM-TMI 300cGy was delivered using a linear accelerator in combination with fludarabine/IV busulfan. To plan IM-TMI, 5 mm-slice CT scanning from top of the head to the mid femur was performed with immobilization using a customized whole body alpha cradle. All bones (excluding the arms and lower extremities) were contoured as the clinical target volume. A 3 mm margin was added to obtain the planning target volume (PTV). The organs at risk (OAR) including the brain, lenses, lungs, liver, kidney, small bowel and heart were identified and contoured. The IM-TMI technique consisted of three separate treatment plans: the head and neck; trunk; and pelvis. Patients received fludarabine 40mg/m2 on days -8 to -5. IV busulfan was given on days -5 to -2 targeting an AUC of 4800microM/min based on a pretransplant test dose. IM-TMI was delivered on day -5. The patients received a total of 300 cGy IM-TMI dose in two fractions, 8 hours apart. Two patients were treated: one is a 63 year old male with multiple myeloma who relapsed within 6 months after an autologous transplant with new cytogenetic abnormalities; and the second is a 52 years old female with AML who failed initial induction chemotherapy and at the time of transplant was in complete remission after receiving a second induction and one consolidation chemotherapy. Both patients received PBSC from HLA matched siblings. IM-TMI technique achieved 95% coverage of the PTV. The mean doses to the lenses and lungs were 99 and 195 cGy, respectively. Overall doses delivered to OAR were reduced by 20–67% on average when compared to standard total body irradiation. Treatment time was 44 min and 32 min for the beam-on and set-up, respectively, using the Varian 21 EX linac and MV imaging. Both patients suffered Bearman grade 1 mucositis. No other extramedullary toxicities were observed. Both engrafted in a timely manner achieving neutrophil >0.5 × 109/L at day 13 and 14, and platelet >20 × 109/L at day 8 and 9, respectively. Full donor chimerism was noted by day +30. After follow up of 246 and 218 days, respectively, both patients are alive and in remission. One developed a grade 2 acute GVHD and none of them has chronic GVHD. This study demonstrates for the first time the use of IM-TMI using a linear accelerator. The possibility of adding higher doses of IM-TMI to a myeloablative regimen without toxicity will be tested in a dose escalating clinical trial. Disclosures: No relevant conflicts of interest to declare.

Stratified Intense-Dose- Yttrium-90 Ibritumumab Tiuxetan (90YIT ) with Bendamustine+Fludarabine Nonmyeloablative Conditioning for Allogeneic Stem Cell Transplantation in b-Cell Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 662-662
Author(s):  
Issa F. Khouri ◽  
Bill Erwin ◽  
Alison M Gulbis ◽  
Francesco Turturro ◽  
S Cheenu Kappadath ◽  
...  
Keyword(s):  
Cord Blood ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Median Number ◽  
Whole Body ◽  
Fixed Dose ◽  
Patient Specific ◽  
Organ Doses ◽  
Significant Difference

Abstract Background: Nonmyeloablative allogeneic transplantation has the potential to induce long-term remissions in patients with relapsed lymphoma. However, a non-intense conditioning regimen enhances the risk of early relapse. Anti-CD20 antibody radioimmunotherapy (90YIT) delivers radiation dose not only to the tumor cells that bind the antibody but also to inaccessible neighboring cells as a result of the cross-fire effect. Thus, we hypothesized that the addition of escalated 90YIT dose to the recently published bendamustine+fludarabine conditioning regimen (Khouri et al. Blood 2014) would facilitate early cytoreduction in such patients and promote improved long-term disease control by the allogeneic graft. Organ doses from a 90YIT weight-based activity prescription (mCi/kg) vary considerably, which justifies a dosimetry-based strategy for mCi/kg escalation. Methods and patients: On days -22 and -14, rituximab was given at 250 mg/m2 preceding 111In ibritumumab and 90YIT administration, respectively. Organ dosimetric assessment was performed based on serial 111In ibritumumab whole body scanning (0, 4, 24, 72 and 144 hours) , to select from among five 90YIT mCi/kg prescriptions (0.5, 0.75, 1, 1.25 or 1.5) that would result in an estimated 10 - 12 Gy dose to the liver, lungs or kidneys. Organ dose was corrected for patient-specific mass, based on a CT volume estimate times 1.03 g/cc for liver and kidneys, and a variable specific gravity for lungs (Simon, J Clin Monit Comput, 2000). Bendamustine 130 mg/m2 plus 30 mg/m2 of fludarabine IV were given daily on days -5 to - 3 prior to transplantation. Tacrolimus and mini-methotrexate (Mycophenolate mofetil in case of cord blood transplantation) were used for GVHD prophylaxis. In addition, thymoglobulin 1 mg/kg IV was given on days -2, and -1 in patients receiving an unrelated donor transplant. Results: Twenty patients were studied. The median age was 58 years (range, 37-71). Lymphoma histologies included: indolent (n=8, 40%), diffuse large cell (n=6; 30%), double-hit (n=2; 10%) and mantle cell (n= 4, 20%). The median number of prior chemotherapies received was 4 (range, 2-7). At study entry, 8 patients (40%) were in complete remission following salvage therapy, 7 (35%) were in partial response, and 5 (25%) had refractory disease. Six of 16 (37.5%) patients tested were PET+. Dosimetry: The most exposed organ was either liver (16 patients) or lungs (4 patients). The distribution among the five 90YIT mCi/kg prescriptions (smallest to largest) was 2, 4, 12, 1 and 1, with a mean of 0.94 ± 0.23 mCi/kg. If all twenty patients were treated at 1 mCi/kg (the most common prescription), the 20 Gy limit employed for 90YIT clinical trials prior to approval would have been exceeded in only one patient for the liver (22.9 Gy) or lungs (20.9 Gy). The maximum liver and lung doses at 0.75 mCi/kg would have been 17.2 and 15.7 Gy, respectively. Transplant outcomes: Fifteen patients (75%) received their transplants from unrelated donors (including 1 mismatched and 2 cord blood), and only 5 (25%) from HLA-compatible siblings. The median number of CD34+ cells infused was 6.2 × 106/kg. Neutrophil counts recovered to > 0.5 × 109/L after a median of 12 days (range, 0-24 days). Platelet counts recovered to > 20 × 109/L after a median of 19 days (range, 9-30 days). By day 30, median donor myeloid and T-cells were 100% (range, 98-100). The cumulative incidence of acute grade 2-4 GVHD and chronic extensive GVHD were 25% (5% for acute grade 3-4) and 32%, respectively. Treatment-related mortality (TRM) rates at day 100 and 1 year after transplantation were 0% and 10%, respectively. The 2 cord blood transplants engrafted with 100% donor cells and none had GVHD. With a median follow-up duration of 14 months (range, 3-34 months), the overall survival and progression-free survival rates were 85% and 70%, respectively. No significant difference in survival or TRM could be detected by age, donor type, histology, disease status, PET status or number of prior therapies. Conclusions: Our results indicate that dose-intense 90YIT combined with fludarabine and bendamustine is a well-tolerated nonmyeloablative allogeneic conditioning for lymphoid malignancies, with promising results of engraftment, GVHD and survival. Our stratified 90YIT prescription results suggest that future studies with a fixed dose of 1 mCi/kg level without dosimetry would have an acceptable radiation risk to vital organs in this setting. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy.

scholarly journals Biomedical photoacoustic imaging

2011 ◽  
Vol 1 (4) ◽  
pp. 602-631 ◽  
Author(s):  
Paul Beard
Keyword(s):  
Optical Imaging ◽  
Ultrasound Imaging ◽  
Spatial Resolution ◽  
Breast Imaging ◽  
Clinical Medicine ◽  
Blood Oxygenation ◽  
Whole Body ◽  
Practical Implementation ◽  
Wide Range

Photoacoustic (PA) imaging, also called optoacoustic imaging, is a new biomedical imaging modality based on the use of laser-generated ultrasound that has emerged over the last decade. It is a hybrid modality, combining the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging. In essence, a PA image can be regarded as an ultrasound image in which the contrast depends not on the mechanical and elastic properties of the tissue, but its optical properties, specifically optical absorption. As a consequence, it offers greater specificity than conventional ultrasound imaging with the ability to detect haemoglobin, lipids, water and other light-absorbing chomophores, but with greater penetration depth than purely optical imaging modalities that rely on ballistic photons. As well as visualizing anatomical structures such as the microvasculature, it can also provide functional information in the form of blood oxygenation, blood flow and temperature. All of this can be achieved over a wide range of length scales from micrometres to centimetres with scalable spatial resolution. These attributes lend PA imaging to a wide variety of applications in clinical medicine, preclinical research and basic biology for studying cancer, cardiovascular disease, abnormalities of the microcirculation and other conditions. With the emergence of a variety of truly compelling in vivo images obtained by a number of groups around the world in the last 2–3 years, the technique has come of age and the promise of PA imaging is now beginning to be realized. Recent highlights include the demonstration of whole-body small-animal imaging, the first demonstrations of molecular imaging, the introduction of new microscopy modes and the first steps towards clinical breast imaging being taken as well as a myriad of in vivo preclinical imaging studies. In this article, the underlying physical principles of the technique, its practical implementation, and a range of clinical and preclinical applications are reviewed.

scholarly journals Dose Prediction Using a Three-Dimensional Convolutional Neural Network for Nasopharyngeal Carcinoma With Tomotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Yaoying Liu ◽  
Zhaocai Chen ◽  
Jinyuan Wang ◽  
Xiaoshen Wang ◽  
Baolin Qu ◽  
...  
Keyword(s):  
Neural Network ◽  
Nasopharyngeal Carcinoma ◽  
Prediction Model ◽  
Convolutional Neural Network ◽  
Patch Size ◽  
Organs At Risk ◽  
Whole Body ◽  
Patient Specific ◽  
Dose Prediction ◽  
The Mean

PurposeThis study focused on predicting 3D dose distribution at high precision and generated the prediction methods for nasopharyngeal carcinoma patients (NPC) treated with Tomotherapy based on the patient-specific gap between organs at risk (OARs) and planning target volumes (PTVs).MethodsA convolutional neural network (CNN) is trained using the CT and contour masks as the input and dose distributions as output. The CNN is based on the “3D Dense-U-Net”, which combines the U-Net and the Dense-Net. To evaluate the model, we retrospectively used 124 NPC patients treated with Tomotherapy, in which 96 and 28 patients were randomly split and used for model training and test, respectively. We performed comparison studies using different training matrix shapes and dimensions for the CNN models, i.e., 128 ×128 ×48 (for Model I), 128 ×128 ×16 (for Model II), and 2D Dense U-Net (for Model III). The performance of these models was quantitatively evaluated using clinically relevant metrics and statistical analysis.ResultsWe found a more considerable height of the training patch size yields a better model outcome. The study calculated the corresponding errors by comparing the predicted dose with the ground truth. The mean deviations from the mean and maximum doses of PTVs and OARs were 2.42 and 2.93%. Error for the maximum dose of right optic nerves in Model I was 4.87 ± 6.88%, compared with 7.9 ± 6.8% in Model II (p=0.08) and 13.85 ± 10.97% in Model III (p&lt;0.01); the Model I performed the best. The gamma passing rates of PTV60 for 3%/3 mm criteria was 83.6 ± 5.2% in Model I, compared with 75.9 ± 5.5% in Model II (p&lt;0.001) and 77.2 ± 7.3% in Model III (p&lt;0.01); the Model I also gave the best outcome. The prediction error of D95 for PTV60 was 0.64 ± 0.68% in Model I, compared with 2.04 ± 1.38% in Model II (p&lt;0.01) and 1.05 ± 0.96% in Model III (p=0.01); the Model I was also the best one.ConclusionsIt is significant to train the dose prediction model by exploiting deep-learning techniques with various clinical logic concepts. Increasing the height (Y direction) of training patch size can improve the dose prediction accuracy of tiny OARs and the whole body. Our dose prediction network model provides a clinically acceptable result and a training strategy for a dose prediction model. It should be helpful to build automatic Tomotherapy planning.

Patient-specific Dose From Megavoltage CT Imaging With a Helical Tomotherapy Unit

2007 ◽  
Vol 69 (3) ◽  
pp. S193-S194 ◽  
Author(s):  
A.P. Shah ◽  
K.M. Langen ◽  
K. Ruchala ◽  
A. Cox ◽  
P.A. Kupelian ◽  
...  
Keyword(s):  
Helical Tomotherapy ◽  
Ct Imaging ◽  
Patient Specific ◽  
Megavoltage Ct

Dynamic Behaviour of Ox Tibial and Femoral Bones: A Comparison With Human Bones

2015 ◽  
Author(s):  
Hesam Hoursan ◽  
Mohammad Taghi Ahmadian
Keyword(s):  
Natural Frequencies ◽  
Experimental Studies ◽  
Ct Scanning ◽  
Mode Shapes ◽  
Patient Specific ◽  
Long Term Stability ◽  
Human Bones ◽  
Animal Bones ◽  
Bending Mode

Finite element models have been widely employed in an effort to quantify the stress and strain distribution around human bones as well as implanted prostheses and to explore the influence of these distributions on their long-term stability. In order to provide meaningful predictions, such models must contain an appropriate reflection of mechanical properties. Detailed geometrical and density information is now readily available from CT scanning. However, there are still many complications regarding patient-specific geometrical differences and bone dynamic behavior in-vivo. Experimental studies on animal bones, due to their convenience and accessibility, have always played a key role in simulating human bone behavior. In current study, a modal experiment has been done on an ox femoral and tibial bones and the results have been compared with those reported from human bones. Results have been obtained in terms of natural frequencies of medio-lateral bending mode shapes and damping ratios, and compared with those obtained by some previous studies. The results suggest similar pattern in modal behavior, but considerable difference between natural frequencies due to geometrical differences. To consider structural damping ratios, due to existence of moisture and marrow in bone in-vivo, samples have been obtained few hours post-mortem and the ratio has been extracted for each natural frequency. Finally, conclusions have been made on the similarity of the models and how to improve the FE models of human tibial and femoral components.

scholarly journals mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1043 ◽  
Author(s):  
Phil Jun Kang ◽  
Daryeon Son ◽  
Tae Hee Ko ◽  
Wonjun Hong ◽  
Wonjin Yun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Human Urine ◽  
Neurological Disorders ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Global Gene Expression ◽  
Patient Specific ◽  
Human Neural Stem Cells

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.

Incorporating Patient-Specific Variability in the Simulation of Realistic Whole-Body $^{18}{\hbox{F-FDG}}$ Distributions for Oncology Applications

2009 ◽  
Vol 97 (12) ◽  
pp. 2026-2038 ◽  
Author(s):  
Amandine Le Maitre ◽  
William Paul Segars ◽  
Simon Marache ◽  
Anthonin Reilhac ◽  
Mathieu Hatt ◽  
...  
Keyword(s):  
Whole Body ◽  
Patient Specific
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