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New England Chapter of AAPM
http://chapter.aapm.org/NE/NE.html
2015 Officers and Board Members
President
President-Elect
Treasurer
Secretary
Officer-at-Large
Representative Board Member
Immediate Past President
Ross Berbeco, PhD
Carla Bradford, PhD
John Lewis, PhD
Gregory Sharp, PhD
Jennifer Pursley, PhD
Paul Imbergamo, MS
David Gierga, PhD
rberbeco@lroc.harvard.edu
carla.bradford@umassmemorial.org
jhlewis@lroc.harvard.edu
gcsharp@mgh.harvard.edu
jpursley@mgh.harvard.edu
pimberga@rtsx.com
dgierga@mgh.harvard.edu
Corporate Membership
IT Committee
Nomination Committee
Meeting Coordination. Committee
CAMPEP Coordinator
Gene Cardarelli, PhD
Jacek Kukluk, PhD
Joseph Killoran, PhD
Martin Fraser, MS
Robert Cormack, PhD
gcardarelli@harthosp.org
jkukluk@lroc.harvard.edu
jkilloran@lroc.harvard.edu
m.fraser@verizon.net
rcormack@lroc.harvard.edu
Dear Colleagues and NEAAPM members:
Snow-mageddon has finally subsided and the long thaw has begun. We have two exciting events
this Spring which you will not want to miss. First, Carla Bradford (NEAAPM President-Elect)
will host the 2015 Peter Neurath Young Investigators Symposium on April 24 in the Jimmy Fund
Auditorium of the Dana-Farber Cancer Institute. CAMPEP has approved 3.5 credits for the
meeting. There is a packed agenda with 25 (!) excellent abstracts presented by the up and coming
stars of our organization. Registration is free for this event. Come support our young
investigators and be sure to stick around for the reception afterwards at The Squealing Pig!
I would also like to invite everyone to attend our Annual Summer Meeting, which is scheduled
for Friday, May 29th at Old Sturbridge Village in Sturbridge, MA. NEAAPM President-Elect
Carla Bradford has put together an outstanding program for this all-day event. CAMPEP
approval is currently in progress. There will be discounted lodging for anyone wishing to stay
over (www.osv.org/inn), please just mention that you are part of the NEAAPM event. There will
also be discounted admission to the village on Saturday – did someone say butter churning
contest? I encourage you to consider registering early via our website, with discounted
registration available until May 22nd (http://chapter.aapm.org/NE).
I look forward to seeing you all this Spring!
Sincerely,
Ross Berbeco
President NEAAPM Agenda
1:00pm – 1:05 Remembering Peter Neurath
New England Chapter of AAPM
Charles Neurath
http://chapter.aapm.org/NE/NE.html
1:00 – 1:30
NEAAPM
Peter Neurath Young Investigators Symposium
Date:
Time:
Location:
Nonequilibrium Nanoscale Ionizing Energy
Deposition and Conversion Phenomena in Medical
Physics
Friday, April 24
1:00 - 5:00 PM
Jimmy Fund Auditorium
Dana-Farber Cancer Institute
35 Binney St., Boston, MA 02115
The Peter Neurath Young Investigators Symposium was created in memory
of Dr. Peter Neurath, who was Director of Medical Physics at the Tufts-New
England Medical Center from 1968 to 1977. Its purpose is to encourage
younger members of the medical physics community to present their
research to their colleagues in the AAPM. “Young” means anyone starting
out in medical physics including trainees, graduate students, post-doctoral
fellows or physicists recently entered into the field.
A winner of the Symposium will be chosen by a panel of three judges based
on the following criteria: clarity, quality and rigor of work, significance,
innovation, timeliness, and interest to the medical physics community.
The NEAAPM YIS is an opportunity for professionals in medical physics to keep up to date on subjects relevant to the field and interact with colleagues from around the New England area. The meeting is intended for physicists, dosimetrists, therapists and others with an interest in medical physics. It is sponsored by the New England chapter of the AAPM. Keynote Presentation:
Erno Sajo, PhD
Professor and Director of Medical Physics
Department of Physics and Applied Physics
University of Massachusetts Lowell
Piotr Zygmanski, PhD
Assistant Professor
Harvard Medical School
BWH / DFCI
1:30 – 3:00
Young Investigator Talks: Session 1
3:00 – 3:05
Special Election for NEAAPM Treasurer
3:00 – 3:30
Coffee Break
3:30 – 5:00
Young Investigator Talks: Session 2
5:00
Speaker Reception at:
The Squealing Pig (134 Smith St.)
CAMPEP approval has been secured for 3.5 MPCECs for this program.
1
Jimmy Fund Auditorium Dana‐Farber Cancer Institute 35 Binney Street, Boston, MA 02115 Driving instructions: http://www.masco.org/directions/car Public transportation: http://www.masco.org/directions/rapid‐transit http://www.masco.org/directions/bus Young Investigator Talks (Session 1):
Young Investigator Talks (Session 2):
1:30 Thomas Ruggieri (MGH)
Improved QA and workflow for proton treatment hardware fabrication
1:37 Davide Brivio (BWH)
Monte Carlo evaluation of Kilovoltage radiosurger the AuNPs for Age
related Macular Degeneration (AMD)
1:44 Brian Ruiz (Alliance Oncology)
A Novel Expansion Method for MRI Based Target Delineation in
Prostate Radiotherapy
1:51 Patrick Grossmann (DFCI/BWH)
Identification of Molecular Phenotypes by Integrating Radiomics and
Genomics
1:58 Xuhua Ren (MGH)
Automated segmentation with post-registration atlas selection based
on mutual information
2:05 Weixing Cai (MGH/BWH)
4DCBCT-Based Dose Assessment for SBRT Lung Cancer Treatment
2:12 Marios Myronakis (BWH)
4DCT Motion Modeling to Predict Motion during Successive Days of
Treatment
2:19 Ramin Abolfath (Yale)
Towards First Principle Modeling of Biological Responses of Ionizing
Radiation
2:26 Thibaud Coroller (BWH/DFCI)
CT-based Volumetric Features are Associated with Somatic Mutations
in Lung Cancer
2:33 Alexandre Detappe (BWH/DFCI)
AGuIX nanoparticles: Advanced Platform for Image-Guided Radiation
Therapy
2:40 Roland Schnuerer (MGH)
In-vivo Beam Range Verification in Proton Therapy with Scanning
Beams
2:47 Susu Yan (MGH)
Are proton gantries needed? An analysis of 4332 patient proton gantry
treatment plans from the past 10 years.
2:54 Hanjoon Cho (URI)
Evaluation of Planned Dose Distributions by Monte Carol (0.5%) and
Ray Tracing Algorithm for the Spinal Tumors with CyberKnife
3:30 Bram Gorissen (MGH)
Robustness versus Plan Quality for Intensity-Modulated Proton
Therapy
3:37 Melissa Spencer (UML)
Cell Survivor: A conceptual model of radiation biophysics using a game
engine
3:44 Yuting Lin (MGH)
Irradiation of Human Cell Lines using Carbon Ions: Real Time
Dosimetry using Gaf-chromic Film
3:51 Inna Gertsenshteyn (BU/MGH)
Comparing Optimized Mutual Information and Gradient
Magnitude Metrics for Deformable Image Registration
3:58 Mohammed Jermoumi (UML)
Dose escalation to biological tumor volumes of prostate cancer
patients using gold nanoparticles
4:05 Linxi Shi (UMass Worcester)
Dedicated cone-beam breast CT with laterally-shifted detector:
Feasibility for clinical translation
4:12 Salam Dhou (BWH)
Dedicated cone-beam breast CT with laterally-shifted detector:
Feasibility for clinical translation
4:19 Teun Minkels (MGH)
Using stylized models to investigate the potential benefit of
inhomogeneous fractionation schemes in proton therapy
4:26 Suman Shrestha (UMass Worcester)
Photon-counting Hexagonal Pixel Array CdTe Detector: Performance
characteristics for high-resolution region-of-interest fluoroscopy
4:33 Garron Deshazer (URI)
Microwave ablation zone variance: Identifying which parameters
should be detected and incorporated in patient specific planning
4:40 Yao Hao (UML)
New potential for employing radiotherapy biomaterials loaded with antiCTLA-4 antibody to induce abscopal effect
4:47 Madan Mainali (UMass Boston/DFCI)
Potential of using cerium oxide nanoparticles (CONP) for protecting
healthy tissue during Accelerated Partial Breast Irradiation (APBI)
3:01 Coffee Break
5:00
Speaker Reception (The Squealing Pig, 134 Smith St.)
2
Improved QA and workflow for proton treatment hardware
fabrication
Monte Carlo evaluation of Kilovoltage radiosurgery with
AuNPs for Age related Macular Degeneration (AMD)
Thomas Ruggieri, B. Sc, Alan Schinazi, M. Sc, Hanne Kooy, Ph.D.
D. Brivio, P. Zygmanski, E. Sajo, G Makrigiorgos, W. Ngwa
Purpose: The original MGH system required a manual management of
requests for patient hardware and often caused delays in patient treatments.
The new system, instead, provides an automated pathway for requests and a
means of verification that the manufactured parts match the treatment plan.
Traceability of the requests adds necessary security that ensures that the
correct parts are made and delivered to the treatment room. The machine-shop
interface is fully automated and web based retrieve programs for the CNC
machines. The new system identifies existing hardware and mates with the
new devices when needed, preventing duplication of existing devices.
Purpose: To evaluate the benefit of gold nanoparticles (AuNP) in radiosurgery
of Age related Macular Degeneration (AMD) using Monte Carlo (MC)
simulation. AMD disease causes vision loss due to a leaky vasculature of the
endothelial cells. Radiosurgical therapy aims to destroy this vasculature while
minimizing the delivered dose to healthy tissues of the eye. AuNP known to
enhance local dose have been targeted to the macular choroidal endothelial
cells to increase the therapeutic efficacy.
Methods: A postgresql database was designed that records each request and
includes complete information about each request. In order to ensure that the
correct versions of the requested hardware are used, a crypto-hash of each
fabrication data file is made this allows us to detect if the data file is tampered
with. Our application detects the new records in the database and
automatically starts an instance of SolidWorks which automatically generates
3-D models of the requested hardware and indicates the status on a web
based GUI. This GUI is accessed by the treatment planners to access a 3-D
image of the model which can be zoomed and rotated. When the model is
constructed, the machinist can use the web UI to add pins to the hardware if
needed and request the tool path. The tool path is automatically generated
using GibbsCam; our application is able to control GibbsCam without human
intervention. The web GUI was written using asp.net and the manager
application that performs all of the automated tasks was written in c#.
Results and Conclusions: The system has been used to manufacture more
than 13,000 sets of hardware over the last four years. Many improvements
have been realized and tracking down errors is much easier. The time from
request to treatment can be under 1 hour for many cases. Control
documentation has also helped identify many instances where the treatment
planning documentation had been generated erroneously, due to manual
processes in the treatment planning process. The introduction of 3-D models
has allowed the use of more sophisticated tool path algorithms which reduced
the time to manufacture a set of hardware by a factor of 3 or more and a
reduction in tooling costs by more than 90%. This has allowed us to increase
our production in the machine shop and at the same time, reduce the number
of full time employees from two to one and use less equipment, three CNC
milling machines down to two.
Methods: Dose enhancement ratio (DER) in macula endothelial cells due to a
thin layer of AuNP has been calculated by a MC radiation transport simulation.
AuNP layer (10-100nm) has been placed on the bottom of the macula at 2.4cm
depth in a water parallelepiped 3x3x6cm3. This layer has been modeled
considering various concentrations of AuNP ranging from 5.5-200mg per gram
of endothelial cell (volume 10x10x2um3). The x-ray source is 100kVp 4mm
diameter beam tilted 0°-30° with respect to the lens.
Results: DER in endothelial cell for AuNP concentration of 31mg/g (shown
experimentally feasible) and 10-100nm sizes is about 1.8. Tilting 4mm-beam
does not reduce the enhancement but allows to avoid the surrounding tissues.
Dose distribution in the AuNP vicinity has a significant increase within 30um,
peaked at AuNP interface. DER inside and outside of the irradiation 4mm-field
are the same while the actual delivered dose is more than one order of
magnitude lower outside the field. Compared to 100kVp, usage of filtered
spectra with enhanced flux in the region 20keV-40keV shows further increase
of DER by about 20%. Dose to the neighboring organs such as retina/optic
nerve are reduced accordingly.
Conclusion: The results of this MC simulation provide further confirmation of
the potential to enhance DER with AuNP from previous analytical calculations.
This study provides impetus to improve treatment effectiveness of AMD
disease with radiotherapy.
3
A Novel Expansion Method for MRI Based Target Delineation
in Prostate Radiotherapy
Identification of Molecular Phenotypes by Integrating
Radiomics and Genomics
Brian Ruiz
Patrick Grossmann, M.Sc., Olya Grove, Ph.D., Nehme El-Hachem M.Sc.,
Emmanuel Rios-Velazquez Ph.D., Chintan Parmar1, M.Sc., Ralph T.H.
Leijenaar M.Sc., Benjamin Haibe-Kains Ph.D., Philippe Lambin M.D, Ph.D.,
Robert J. Gillies Ph.D., Hugo J.W.L. Aerts Ph.D.
Purpose: To compare a novel bladder/rectum carveout expansion method on
MRI delineated prostate to standard CT and expansion based methods for
maintaining prostate coverage while providing superior bladder and rectal
sparing.
Methods: Ten prostate cases were planned to include four trials: MRI vs CT
delineated prostate/proximal seminal vesicles, and each image modality
compared to both standard expansions(8mm 3D expansion and 5mm
posterior, i.e. ~8mm) and carve out method expansions (5mm 3D
expansion, 4mm posterior for GTV–CTV excluding expansion into
bladder/rectum followed by additional 5mm 3D expansion to PTV, i.e. ~1cm).
All trials were planned to total dose 7920 cGy via IMRT. Evaluation and
comparison was made using the following criteria: QUANTEC constraints for
bladder/rectum including analysis of low dose regions, changes in PTV volume,
total control points, and maximum hot spot.
Results: ~8mm MRI expansion consistently produced the most optimal plan
with lowest total control points and best bladder/rectum sparing. However, this
scheme had the smallest prostate (average 22.9% reduction) and subsequent
PTV volume, consistent with prior literature. ~1cm MRI had an average PTV
volume comparable to ~8mm CT at 3.79% difference. Bladder QUANTEC
constraints were on average less for the ~1cm MRI as compared to the ~8mm
CT and observed as statistically significant with 2.64% reduction in V65. Rectal
constraints appeared to follow the same trend. Case-by-case analysis showed
variation in rectal V30 with MRI delineated prostate being most favorable
regardless of expansion type. ~1cm MRI and ~8mm CT had comparable plan
quality.
Conclusion: ~8mm MRI had the smallest PTV leading to margins that may be
too tight. Bladder/rectum carveout expansion method on MRI delineated
prostate was found to be superior to standard CT based methods in terms of
bladder and rectal sparing while maintaining prostate coverage. Continued
investigation is warranted for further validation.
Purpose: To uncover the mechanistic connections between radiomic features,
molecular pathways, and clinical outcomes, to develop radiomic based
predictors of pathway activation states in individual patients, and to assess
whether combining radiomic with clinical and genomic data improves
prognostication.
Methods: We analyzed two independent lung cancer cohorts totaling 351
patients, for whom diagnostic computed tomography (CT) scans, geneexpression profiles, and clinical outcomes were available. The tumor
phenotype was characterized based on 636 radiomic features describing tumor
intensity, texture, shape and size. We performed an integrative analysis by
developing and independently validating association modules of coherently
expressed radiomic features and molecular pathways. These modules were
statistically tested for significant associations to overall survival (OS), TNM
stage, and pathologic histology.
Results: We identified thirteen radiomic-pathway association modules (p <
0.05), the most prominent of which were associated with the immune system,
p53 pathway, and other pathways involved in cell cycle regulation. Eleven
modules were significantly associated with clinical outcomes (p < 0.05). Strong
predictive power for pathway activation states in individual patients was
observed using radiomics; the strongest per module predictions ranged from
an intra-tumor heterogeneity feature predicting RNA III polymerase
transcription (AUC 0.62, p = 0.03), to a tumor intensity dispersion feature
-6
predicting pyruvate metabolism and citric acid TCA cycle (AUC 0.72,p<10 ).
Stepwise combinations of radiomic data with clinical outcomes and gene
expression profiles resulted in consistent increases of prognostic power to
predict OS (concordance index max = 0.73, p < 10-9).
Conclusion: This study demonstrates that radiomic approaches permit a
non-invasive assessment of molecular and clinical characteristics of tumors,
and therefore have the unprecedented potential to cost-effectively advance
clinical decision-making using routinely acquired, standard-of-care imaging
data. We show that prognostic value complementary to clinical and
genomic information can be obtained by radiomic strategies.
4
Automated segmentation with post-registration atlas
selection based on mutual information
4DCBCT-based dose assessment for SBRT lung cancer
treatment
Xuhua Ren, Gregory C Sharp, and Hao Gao
Weixing Cai
Purpose: The delineation of targets and organs-at-risk is a critical step during
image-guided radiation therapy, for which manual contouring is the gold
standard. However, it is often time-consuming and may suffer from intra- and
inter- rater variability. The purpose of this work is to investigate the automated
segmentation.
Purpose: To develop a 4DCBCT-based dose assessment method for
calculating actual delivered dose for patients with significant respiratory motion
during the course of SBRT or anatomical changes between treatment days.
Methods: The automatic segmentation here is based on mutual information
(MI), with the atlas from Public Domain Database for Computational Anatomy
(PDDCA) with manually drawn contours.
Using dice coefficient (DC) as the quantitative measure of segmentation
accuracy, we perform leave-one-out cross-validations for all PDDCA images
sequentially, during which other images are registered to each chosen image
and DC is computed between registered contour and ground truth. Meanwhile,
six strategies, including MI, are selected to measure the image similarity, with
MI to be the best.
Then given a target image to be segmented and an atlas, automatic
segmentation consists of: (a) the affine registration step for image positioning;
(b) the active demons registration method to register the atlas to the target
image; (c) the computation of MI values between the deformed atlas and the
target image; (d) the weighted image fusion of three deformed atlas images
with highest MI values to form the segmented contour.
Results: MI was found to be the best among six studied strategies in the
sense that it had the highest positive correlation between similarity measure
(e.g., MI values) and DC. For automated segmentation, the weighted image
fusion of three deformed atlas images with highest MI values provided the
highest DC among four proposed strategies.
Conclusion: MI has the highest correlation with DC, and therefore is an
appropriate choice for post-registration atlas selection in atlas-based
segmentation.
Methods: To address the limitation of 4DCT-based dose assessment, we
propose to calculate the delivered dose using time varying (‘fluoroscopic’) 3D
patient images generated from a 4DCBCT-based motion model. The method
includes four steps: (1) before each treatment, 4DCBCT data is acquired with
the patient in treatment position, based on which a patient-specific motion
model is created using a principal components analysis (PCA) algorithm. (2)
During treatment, 2D time-varying kV projection images are continuously
acquired, from which time-varying ‘fluoroscopic’ 3D images of the patient are
reconstructed using the motion model. (3) Lateral truncation artifacts are
corrected using planning 4DCT images. (4) the 3D dose distribution is
computed for each timepoint in the set of 3D fluoroscopic images, from which
the total effective 3D delivered dose is calculated by accumulating deformed
dose distributions. This approach is validated using six modified XCAT
phantoms with lung tumors and different respiratory motions derived from
patient data. The estimated doses are compared to that calculated using
ground-truth XCAT phantoms.
Results: For each XCAT phantom, the delivered tumor dose values generally
follow the same trend as that of the ground truth and at most timepoints the
difference is less than 5%. For the overall delivered dose, the normalized error
of calculated 3D dose distribution is generally less than 3% and the tumor D95
error is less than 1.5%.
Conclusions: XCAT phantom studies indicate the potential of the proposed
method to accurately estimate 3D tumor dose distributions for SBRT lung
treatment based on 4DCBCT imaging and motion modeling. Further research
is necessary to investigate its performance for clinical patients data.
5
4DCT motion modeling to predict motion during successive
days of treatment
Towards First Principle Modeling of Biological Responses of
Ionizing Radiation
Marios Myronakis, Weixing Cai, Salam Dhou, Fulya Cifter, John Lewis
Ramin Abolfath, Yale School of Medicine
Purpose: To quantify the accuracy of motion modeling during simulation, using
external-surrogate measurements to enhance prediction of motion during
successive days of treatment.
Purpose: To develop a novel computational approach to enable researchers to
study the real-time DNA damage-repair pathway in-silico and the
radiobiological effectiveness of photon beams, charged particles, and heavy
ions.
Method and Materials: 4DCT images were generated by combining the XCAT
phantom with measured internal and external motion from patients that
underwent lung cancer with conventional radiotherapy treatment (Hokkaido
dataset). Each phantom included a tumor of 20 mm. Breathing and tumor
motion were implemented according to the corresponding Hokkaido data for
each patient. Three-dimensional (3D) tumor trajectories extracted from the
XCAT phantom and the respective measured external surrogate motion from
several days of lung cancer treatment were utilized to evaluate the ability of our
motion modeling techniques to predict the dose and duty cycle of gating or
tracking treatments. Measured data and simulated tumor motion from the first
day were used to construct the motion models and calculate the duty cycle and
residual tumor for successive days of treatment.
Methods: First principle modeling of biological responses of ionizing radiation
based on the computational integration of Monte Carlo track structure of the
energy deposition in sub-atomic scale with the molecular dynamics of
biomolecules, proteins, DNA and nano-structures.
Results: Preliminary calculations of duty cycle and residual tumor motion were
performed on measured data for four patients at 25% and 50% gating window
and two days of treatment. The range of duty cycle values was 22.08% to
25.00% and 44.17% to 50.00% for 25% and 50% gating window respectively.
Inter-fraction change was between -6.6% and 4.7% for both gating windows.
The residual tumor motion ranged from 6.06 to 11.40 mm at 25% and from
3.40 to 8.34 mm at 50% window. Inter-fraction change of residual tumor motion
varied widely and found between -5.7% to 75.3% with the highest value
obtained at 50% window.
Results: For illustration of the methodology, the predicted population of DSBs
along the proton track with the highest occurrence frequency in the Bragg peak
and a quantitative comparison demonstrating the agreement between
theoretical predictions and more recently reported experimental data based on
counting will be discussed.
Conclusion: The measurements of the relative biological effectiveness of the
proton beam have revealed the dependence of the DSB induction on the beam
energy, LET, depth and dose. The present computational model exhibits
consistent agreement with the experimental data.
Conclusion: Motion modeling during simulation may be used to predict the
dose and duty cycles of gating and tracking treatments.
6
CT-based volumetric features are associated with somatic
mutations in lung cancer
AGuIX nanoparticles: Advanced platform for image-guided
radiation therapy
T.P. Coroller, P. Grossmann, Y. Hou, S.W. Lee, R.H. Mak, H.J.W.L Aerts
Alexandre Detappe, Sijumon Kunjachan, Olivier Tillement, Ross Berbeco
Purposes: Subsets of non-small cell lung cancer (NSCLC) are driven by
mutations in key oncogenes, with unique biology including susceptibility to
targeted treatment. Additionally, those mutations could lead to phenotypic
differences of the primary tumor that can be assess with quantitative imaging.
In this study, we investigated whether somatic mutation are associated with,
and hence can be predicted by CT tumor volume-based features of NSCLC
patients.
Methods: We included 117 NSCLC patients with treatment-planning CT scans
in our analysis and clinical genotyping for the epidermal growth factor receptor
(EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) oncogenes.
We extracted four volumetric features describing volume and diameters (x/y
axis and 3D) of the primary tumor. Volumetric differences between mutant and
wild-type tumors were assessed using Wilcoxon test. Predictive value of the
volumetric features for mutation status was assessed using the area under the
curve (AUC).
Results: Genotype distribution included 14 (12%) EGFR mutant, 35 (30%)
KRAS mutant, and 68 (58%) wild-type tumors. All volumetric features for EGFR
mutant were significantly (p-value <0.05) lower than for KRAS mutant and
Wild-Type. No volumetric features were significantly different between KRAS
and Wild-Type. The median (Q1-Q3) for volume was 10.2(6.1-29.6), 39.3(14.389.7) and 49(10.7-119) for EGFR, KRAS and Wild-Type respectively. All
volumetric features were also significant predictive features for EGFR mutation
with median (range) AUC of 0.69(0.67-0.70) and all p-value<0.05. However,
the AUC was only 0.51(0.50-0.51) for KRAS mutation.
Purpose: AGuIX are advanced gadolinium-based nanoformulation developed
for combined MR imaging and radiation therapy. We explored the potential of
these hybrid nanoparticle to investigate its radiation dose enhancement ability
during radiation with the aid of noninvasive MR imaging.
Methods: We performed in vitro cell uptake and radiosensitization studies of a
pancreatic cancer cell line in a low energy (220kVp) beam, a standard clinical
6MV beam (STD) and a flattening filter free clinical 6MV beam (FFF). After
injection of 40mM of nanoparticles, a biodistribution study was performed in
vivo on mice with subcutaneous xenograft pancreatic tumors. In vivo radiation
therapy studies were performed at the time point of maximum tumor uptake.
Results: The concentration of AGuIX nanoparticles in Panc-1 pancreatic
cancer cells, determined in vitro by MRI and ICPMS, peaks after 30 minutes
with 0.3% of the initial concentration (5mg/mL). Clonogenic assays show a
significant effect (p<0.05) when the AGuIX are coupled with MV photon
irradiation (DEF20%=1.31). Similar AGuIX tumor uptake is found in vivo by
both MRI and ICPMS 30 minutes after intravenous injection of 40mg/mL of
AGuIX. For long term survival studies, the choice of the radiation dose is
determined with 5 control groups (3mice/group) irradiated with 0, 5, 10, 15, and
20Gy. Afterwards, 4 groups (8mice/group) are used to evaluate the effect of
the nanoparticles. A Logrank test is performed as a statistical test to evaluate
the effect of the nanoparticles.
Conclusion: The combination of the MRI contrast and radiosensitization
properties of gadolinium nanoparticles reveals a strong potential for usage with
MRI-guided radiation therapy.
Conclusions: EGFR mutant primary tumors were significantly smaller (for all
volumetric features) than KRAS or Wild-Type. Moreover, all volumetric features
were significantly predictive for EGFR. KRAS and Wild-type could not be
discriminated only based on volumetric features. A larger set of imaging
features (e.g. Radiomics) would help find more predictive biomarkers for tumor
mutation status
7
In-vivo beam range verification in proton therapy with
scanning beams
Are proton gantries needed? An analysis of 4332 patient
proton gantry treatment plans from the past 10 years.
Roland Schnuerer, Nicolas Depauw, Tarek Halabi, El Hassane Bentefour,
Benjamin Clasie, Thomas Bortfeld and Hsiao-Ming Lu
Susu Yan, Hsiao-Ming Lu, Jay Flanz, Nicolas Depauw, Judith Adams, Bram L.
Gorissen, Yi Wang, Juliane Daartz, Thomas Bortfeld
Purpose: Uncertainties in treatment planning or patient anatomy limit the use
of the well-defined range of the Bragg-peak as the most outstanding
characteristic in proton therapy. In-vivo beam range verification offers the
feasibility to overcome these uncertainties and improve proton treatment.
Energy resolved point dose measurements are explored for range verification
in scanning systems.
Purpose: To ascertain the necessity of a proton gantry, as compared to the
feasibility of using horizontal fixed proton beam-line for treatment with
advanced technology.
Methods: The unique behavior of dose per depth of the irradiated volume
against the energy of the used set of proton beams allows extracting the waterequivalent path length (WEPL) for range verification. Computed energy
resolved dose functions by using Monte Carlo serve as a calibration field and
as the source for performing numerical dose distribution simulations. The
WEPL is determined by pattern matching of the energy resolved dose function
using a least square fit against a library of energy resolved dose functions of
the pre-established calibration field. Validating this method and determining the
accuracy of the WEPL values by investigating crucial characteristics of the
beam field (number of energy layers, energy spacing) in terms of uncertainties
are the aims of the examined simulation. Approaches to reduce the applied
dose of the field are also presented.
Results: The performed dose distribution simulations proved the method of
energy resolved dose measurement and show the capability to determine the
WEPL precisely with sub-millimeter accuracy with a ‘scout’ field with e.g. 4
energy layers and a spacing of 2.5 mm between the layers. Increasing the spot
spacing up to 1.75 cm reveals the potential to reduce the applied dose by still
having a sufficient uniform energy layer.
Conclusion: Energy resolved dosimetry indicates a clinical potential for in-vivo
range verification for proton scanning treatment. Simulations demonstrated that
the accuracy of the retrieved WEPL meets clinical requirements. Further, the
method has to be verified in water and for tissue heterogeneities (range
mixing).
Methods: To calculate the percentage of patients that can be treated with a
horizontal fixed beam-line instead of a gantry, we analyze the distributions of
beam orientations of our proton gantry patients treated over the past 10 years.
We identify three horizontal fixed beam geometries (FIXED, BEND and MOVE)
with the patient in lying and/or sitting positions. The FIXED geometry includes
only table/chair rotations and translations. In BEND, the beam can be bent
up/down for up to 20 degrees. MOVE allows for patient head/body angle
adjustment. Based on the analysis, we select 8 patients whose plan involves
beams which are still challenging to achieve with a horizontal fixed beam.
These beams are removed in the pencil beam scanning (PBS) plan optimized
for the fixed beam-line (PBS-fix). We generate non-coplanar PBS-gantry plans
for comparison, and perform a robustness analysis.
Results: The percentage of patients with head-and-neck/brain tumors that can
be treated with horizontal fixed beam is 44% in FIXED, 70% in 20-degrees
BEND, and 100% in 90-degrees MOVE. For torso regions, 99% of patients can
be treated in 20-degree BEND. The target coverage is more homogeneous
with PBS-fix plans compared to the clinical scattering treatment plans. The
PBS-fix plans reduce the mean dose to organs-at-risk by a factor of 1.1-28.5.
PBS-gantry plans are as good as PBS-fix plans, sometimes marginally better.
Conclusions: The majority of the beam orientations can be realized with a
horizontal fixed beam-line. Challenging non-coplanar beams can be eliminated
with PBS delivery. Clinical implementation of the proposed fixed beam-line
requires use of robotic patient positioning, further developments in
immobilization, and image guidance. However, our results suggest that fixed
beam-lines can be as effective as gantries.
8
Evaluation of Planned Dose Distributions by Monte Carlo
(0.5%) and Ray Tracing Algorithm for the Spinal Tumors with
CyberKnife
Robustness versus plan quality for intensity-modulated
proton therapy
Hanjoon Cho, James Brindle PhD, and Jaroslaw Hepel MD
Bram L. Gorissen, Nicolas Depauw, Jan Unkelbach
Purpose: To analyze and evaluate dose distribution between Ray Tracing (RT)
and Monte Carlo (MC) algorithms of 0.5% uncertainty on spinal cord, gross
target volume (GTV) and planning target volume
(PTV) for the treatment of spinal tumors.
Purpose: Range and set-up uncertainties in intensity-modulated proton
therapy cannot be addressed with margins. Instead, several robust
optimization (RO) models have been developed that explicitly take uncertainty
into account. RO optimizes the worst case at the cost of the treatment outcome
in more likely scenarios. The goal is to provide insight in the trade-off between
robustness and plan quality and the behavior of different trade-off methods.
Methods and Materials: Twenty four spinal tumor patients were treated with
stereotactic body radiotherapy (SBRT) by CyberKnife in 2013 and 2014. The
MC algorithm with 0.5% of uncertainty is used to recalculate the dose
distribution for the treatment plan of the patients using the same beams, beam
directions, and monitor units (MUs).
Results: The maximal doses are uniformly larger for MC plans than RT
calculations except one case. Maximal irradiated doses on spinal cord
calculated by MC algorithm are larger than calculations by RT algorithm except
3 cases for the volume of <0.25 cc and 4 cases for the volume of <1.2cc out of
23 cases. The difference is 0.93 Gy on average and 3.1 Gy in maximum for the
volume of <0.25cc, and 0.62 Gy on average and 2.1 Gy in maximum for the
volume of <1.2cc. The MC calculated dose covering 100% of the PTV or GTV
is greater than the RT calculation in dose volume histogram (DVH) from the
ratio of D100 calculated by MC and RT for both PTV and GTV. However there
are not much dose difference covering 90 % of the PTV and GTV between
calculations by MC and RT. There are almost no conformity change between
the calculations by MC and RT.
Conclusions: The MC recalculated dose distributions on spinal cord are larger
than the original RT calculations for the spinal tumor treatments. Based on the
greater accuracy of MC-based treatment planning, we might save the dose on
spinal cord when treating tumors in spinal region. We might at least benefit
from saving the irradiation dose on spinal cord by considering this study when
RT algorithm is used because of restrictions of time of treatment planning
calculation by the MC algorithm
Methods: We present four methods to trade-off robustness with plan quality
that can be applied to any of the worst case methods found in literature.
Each trade-off is a mixture between worst case, expected value, and nonrobust planning, which effectively corresponds to assigning different
importance weights to error scenarios. Each method is tested on several worst
case methods for a sarcoma case, a paraspinal case and a benchmark case
from literature.
Results: Each trade-off method yields a unique dose distribution in the border
region between target volume and adjacent normal tissues, corresponding to a
specific trade-off between robustness and nominal plan quality. The fully robust
solutions perform badly when the realized errors are smaller than the maximum
projected errors. Compared to fully robust solutions, significant improvements
are possible for non-extreme scenarios while only slightly deteriorating plan
quality at an extreme scenario. It is further observed that trade-off methods
cannot be mimicked by putting different weights on objectives for the tumor and
the normal tissue.
Conclusion: The method to trade-off robustness with plan quality should be
chosen carefully, as each method has a different impact on plan quality. Two of
the methods can directly be implemented in any framework for multicriteria
optimization, hopefully leading to their quick dissemination.
9
Cell Survivor: A conceptual model of radiation biophysics
using a game engine
Irradiation of Human Cell Lines using Carbon Ions: Real Time
Dosimetry using Gaf-chromic Film
Melissa Spencer, Erno Sajo
Yuting Lin, Chiara La Tessa, Adam Rusek and Kathryn D. Held
Purpose: Certain types of radiation biology experiments are modeled within a
game engine, enhancing a player's intuitive understanding and ability to model
complex radiobiological processes. The player of the game acts as the cell's
enzymatic repair process. The simulation is based on published data and a
combination of real-time and pre-computed radiation interactions and energy
deposition processes by deterministic and Monte Carlo kernels.
Methods: A complex simulation incorporates time-dependent dose rate
effects, cell cycle and enzymatic processes, and LET of the radiation. Single
and double strand breaks (SSB and DSB) occur in cells as they are damaged
by radiation. The player repairs SSBs as quickly as possible, and decides to
repair DSBs using either non-homologous end joining or homologous repair,
depending on the situation. Environmental conditions (oxygen, radioprotectors,
sensitizers, etc.) can modify cell behavior and radiation susceptibility. Rest
times demonstrate the purpose of dose fractionation.
Results: A playable prototype has been completed and well known
experiments have been replicated from first principles. The player also gains
an intuitive understanding of the damage done to cells by different types of
radiation and under different conditions, including the mediating effects of
chemicals and can investigate new situations involving combinations of these
effects. Data collected during play can be averaged together as a distributed
Monte Carlo simulation. Shoulders appear on survival curves collected in this
way, and reappear after rest times.
Conclusion: Cell Survivor! shows promise as both an educational tool and a
research tool. Levels can be created specifically to teach laypeople about the
risks of certain kinds of radiation, for instance dental x-rays as compared to CT
scans. Altering the numerous parameters involved in the model allows
investigation of how conceptual assumptions lead to observed outcomes.
Purpose: The purpose of this study is to investigate and quantify several
factors affecting biological effects of carbon ions such as cell type, dose,
energy and position where the cells are irradiated along the pristine Bragg
curve.
Methods: Experiments to quantify clonogenic cell survival in three human lung
cancer cell lines and a fibroblast cell line were performed at the NASA Space
Radiation Laboratory, BNL, Upton, USA. A system of water or media-filled T25
flasks lined up along the beam axis was designed so that the cell-containing
surfaces of the flasks were placed at specific depths along the Bragg curve.
Gaf-chromic films were placed between the flasks to monitor the dose
distribution in the sample as soon as the irradiation was finished. Additional
studies were conducted at four selected depths along the Bragg curve to obtain
full cell survival dose response curves for the four cell lines.
Results: The percent depth dose of the beams was determined using an
ionization chamber and showed that the physical Bragg peak is at 22.5 cm
water depth. However, the clonogenic cell survival data indicated that the
maximum cell killing occurred at 21.5 cm. Gaf-chromic films revealed some
inhomogeneity in the dose distribution on the flasks near the peak, presumably
due to lack of scattering from the sides of the flasks, which might account for
the differences. Depending on the cell line and radiation dose, the maximum
cell killing (i.e., the greatest RBE) is at the 21.5 (the peak) or 24 cm (distal fall
off) depth.
Conclusion: There is a difference in biological effect along the Bragg curve of
a carbon ion beam, indicating an elevated RBE at or beyond the end of the
range. Gaf-chromic films are proven to be effective in monitoring the 2D
irradiation pattern to the flasks.
10
Comparing Optimized Mutual Information and Gradient
Magnitude Metrics for Deformable Image Registration
Dose escalation to biological tumor volumes of prostate
cancer patients using gold nanoparticles
Inna Gertsenshteyn, Neelam Tyagi, Reza Farjam, Aditya Apte, Gregory C.
Sharp
M Jermoumi, E Sajo, H Korideck, W Ngwa
Purpose: Deformable image registration between CT and MRI remains a
challenge due to variability in contrast, homogeneity, and field of view. This
study aims to determine whether an optimized Mutual Information (MI) or
optimized Gradient Magnitude (GM) metric provides favorable results in the
head and neck region.
Methods: Head and neck CT and MR images were acquired for 10 patients as
part of an MRI simulation study with a dual echo mDixon (in phase) T1 fast
field echo sequence. Each pair of scans is registered with MRI as the reference
image using the GM and MI metrics. GM was optimized by non-linear contrast
enhancement, while MI was optimized by controlling histogram parameters.
Results are observed visually, and quantitatively measured by comparing Dice
coefficient and Hausdorff distance of manually contoured bone structures.
Results: Using the optimized GM metric, the average Dice coefficient is 0.61 ±
0.10; the average Hausdorff distance is 2.62 ± 1.2 mm. Using the optimized MI
metric, the average Dice coefficient is 0.58 ± 0.12; the average Hausdorff
distance is 2.9 ± 1.2 mm.
Conclusions: While both metrics performed similarly, the GM metric has a
higher Dice coefficient than the MI metric, and its Hausdorff distance is
marginally lower. This suggests image registration with the optimized Gradient
Magnitude metric may be preferred.
Purpose: Studies have shown that radiation boosting could help reduce
prostate cancer (PCa) recurrence. Biological tumor volumes (BTV) are a high
priority for such radiation boosting. The purpose of this study is to investigate
the potential of radiation boosting of real patient BTVs using gold nanoparticles
(GNP) released from gold-loaded brachytherapy spacers (GBS) during
brachytherapy.
Method: The BTVs of 12 patients having prostate adenocarcinoma identified
with positron emission tomography (PET) and CT scanner using C-11 labeled
tracer [11C]acetate were investigated. The initial GNP concentration and time
to achieve a dose enhancement effect (DEF) of 2 was simulated using the
freely downloadable software RAID APP. The investigations were carried out
for low dose rate (LDR) brachytherapy sources (BTS) described in AAPM Task
Group report 43: Cs-131, I-125, and Pd-103. In first case, we used 7 mg/g and
18 mg/g of GNP initial concentrations to estimate the time needed for released
GNP to achieve a DEF of 2 for the different BTS, and compare with clinically
relevant treatment times. In second case, we calculated the initial
concentration of GNPs needed to achieve a DEF of 2 during the time the BTS
would typically deliver 50%, 70% and 90% of the total dose.
Results: For an initial concentration of 18 mg/g, when using Cs-131, and Pd103, a DEF of 2 could only be achieved for BTV of 3.3 cm3 and 1 cm3
respectively. Meanwhile a DEF of 2 could be achieved for all 12 BTVs when
using I-125. To achieve a DEF of 2 for all patients using Cs-131 and Pd-103,
much higher initial concentrations would have to be used than have been
typically employed in pre-clinical studies.
Conclusion: The I-125 is the most viable BTS that can be employed with
GBS to guide dose painting treatment planning for localized PCa.
11
3D fluoroscopic image generation from patient-specific
4DCBCT-based motion models derived from physical
phantom and clinical patient images
Dedicated cone-beam breast CT with laterally-shifted
detector: Feasibility for clinical translation
Linxi Shi, Srinivasan Vedantham,Souleymane Konate and Andrew Karellas
Purpose: To determine the feasibility of laterally-shifted detector geometry for
high-resolution dedicated cone-beam breast CT (CBBCT) in terms of artifacts,
mean glandular dose (MGD) and x-ray scatter.
Methods: High-resolution, low-noise and high frame-rate detector with minimal
dead-space at chest-wall could be of benefit for CBBCT. However, the field-ofview (FOV) for available detectors is smaller than that used in FDA approved
system. Hence, we investigated the feasibility of laterally-shifted detector
geometry for CBBCT. Full-fan ( 2 f  24 ) clinical projection datasets
acquired with 40x30cm detector were truncated along the fan-beam direction to
f  f ( f  {0.25,1.5, 2.7} ) to emulate the smaller FOV detector.
Ramp-filtered FDK was used to reconstruct the full-fan and the truncated
projection datasets after applying three weighting schemes. Monte Carlo
simulations (GEANT4) were used to record the energy deposited in the breast
and the position-dependent primary and scatter x-ray photon fluence incident
on the detector and hence the scatter-to-primary ratio (SPR). Semi-ellipsoidal
breasts (10/14/18-cm diameter) with varying fibroglandular weight fraction (
were modeled. Mono-energy photons were simulated and weighted for 2
spectra (49kVp, 1.4-mm Al HVL; 60kVp, 3.76-mm Al HVL).
fg
Results: Compared to CBBCT with full-fan, the artifacts from truncated fan at
f  1.5 were subtle. For matched technique factors between full-fan and
truncated fan, Monte Carlo derived MGD indicated 30% ( f  1.5 ) and 21%
( f  2.7 ) reduction with truncated fan. 60kVp reduced SPR by 21-25%
compared to 49kVp. Peak SPR for CBBCT (60kVp) with truncated fan
( f  2.7 ) were 0.09/0.25/0.73 for 10/14/18-cm diameter breasts. The
locations of the peak scatter were laterally-shifted by 14/38/70-pixels for
10/14/18-cm diameter breasts and were not statistically different from the
corresponding theoretically estimated shifts (p=0.47, 2-tailed paired-ratio ttest).
Conclusion: CBBCT with laterally-shifted detector geometry is feasible and
can reduce mean glandular dose and SPR. If residual scatter needs
correction, the location corresponding to scatter-peak can be analytically
computed.
)
Salam Dhou, Weixing Cai, Martina Hurwitz, Christopher Williams, Joerg
Rottmann, Pankaj Mishra, Marios Myronakis, Fulya Cifter, Ross Berbeco, Dan
Ionascu, and John Lewis
Purpose: Respiratory-correlated cone-beam CT (4DCBCT) images acquired
immediately prior to treatment have the potential to represent patient motion
patterns and anatomy during treatment, including both intra- and inter-fractional
changes. We develop a method to generate patient-specific motion models
based on 4DCBCT images acquired with existing clinical equipment and used
to generate time varying volumetric images (3D fluoroscopic images)
representing motion during treatment delivery.
Methods: Motion models are derived by deformably registering each 4DCBCT
phase to a reference phase, and performing principal component analysis
(PCA) on the resulting displacement vector fields. 3D fluoroscopic images are
estimated by optimizing the resulting PCA coefficients iteratively through
comparison of the cone-beam projections simulating kV treatment imaging and
digitally reconstructed radiographs generated from the motion model. Patient
and physical phantom datasets are used to evaluate the method in terms of
tumor localization error compared to manually defined ground truth positions.
Results: 4DCBCT-based motion models were derived and used to generate
3D fluoroscopic images at treatment time. For the patient datasets, the average
tumor localization error and the 95th percentile were 1.57 and 3.13 respectively
in subsets of four patient datasets. For the physical phantom datasets, the
average tumor localization error and the 95th percentile were 1.14 and 2.78
respectively in two datasets. 4DCBCT motion models are shown to perform
well in the context of generating 3D fluoroscopic images due to their ability to
reproduce anatomical changes at treatment time.
Conclusion: This study showed the feasibility of deriving 4DCBCT-based
motion models and using them to generate 3D fluoroscopic images at
treatment time in real clinical settings. 4DCBCT-based motion models were
found to account for the 3D non-rigid motion of the patient anatomy during
treatment and have the potential to localize tumor and other patient anatomical
structures at treatment time even when inter-fractional changes occur.
12
Using stylized models to investigate the potential benefit of
inhomogeneous fractionation schemes in proton therapy
T. Minkels, J. Unkelbach
Purpose: In current practice, radiation fields and fractionation schemes for
intensity-modulated proton therapy (IMPT) are optimized independently.
Simultaneously optimizing the beam intensities and the fractionation scheme
can result in non-uniform spatiotemporal dose delivery, i.e. delivering distinct
dose distributions in different fractions. This may improve the therapeutic ratio
if similar doses are delivered to healthy tissues while delivering high singlefraction doses to parts of the tumor. In this work, simplified models are being
used to find the potential gain of inhomogeneous fractional doses (IFD) and its
dependence on model parameters.
Methods: The beam intensities of multiple pristine Bragg peaks for two
fractions were simultaneously optimized with respect to the biologically
equivalent dose (BED). Objective functions and constraints were chosen such
that the mean BED is minimized in healthy tissues, while delivering a
prescribed BED to tumor voxels. The optimization was performed for three
models: using a single beam, two opposing beams resembling prostate
treatments, and two perpendicular beams that resemble spinal metastasis
treatments.
Results: In all models studied, inhomogeneous fractionation has the potential
to decrease the mean BED in healthy voxels, compared to uniform
fractionation, while delivering the same prescribed BED to tumor voxels. While
hypofractionation is the optimal solution for tumors with a low / -ratio and
uniform fractionation is optimal for tumors with high / -ratio, IFD treatments
are optimal in between. The amount of reduction in mean BED in healthy
voxels for IFD depends on the dose per fraction, the position of the healthy
voxels with respect to the tumor and the beam geometry.
Conclusion: It has been shown that, for suitable geometries, IFD can improve
the therapeutic ratio. Also the parameters for which IFD is the optimal
treatment have been investigated and the reduction in mean BED in healthy
tissue has been expressed in terms of these parameters.
Photon-counting Hexagonal Pixel Array CdTe Detector:
Performance characteristics for high-resolution region-ofinterest fluoroscopy
Suman Shrestha, Srinivasan Vedantham and Andrew Karellas
Purpose: To determine the objective performance characteristics of a
hexagonal pixel array photon-counting CdTe detector under fluoroscopic
conditions.
Methods: A 650・m thick CdTe Schottky photon-counting detector capable of
concurrently acquiring up to 3 energy-windowed images was operated in a
single energy-window mode to include 10 KeV photons. The detector had
hexagonal pixels with apothem of 30・m resulting in pixel spacing of 60・m and
51.96・m along the two orthogonal directions. The detector was characterized
under IEC-RQA5 conditions. Images of a tungsten edge test device were
acquired. The edge-spread function (ESF) and the finely sampled line spread
function accounted for hexagonal sampling, from which the presampling
modulation transfer function (MTF) was determined. The 2-D noise power
spectra (NPS) were determined at fluoroscopic exposure rates (0.77-7.7
・R/frame) from parallelogram regions-of-interest (ROIs) to provide equispaced
sampling. The detective quantum efficiency (DQE) was determined along the
apothem direction after correcting for image lag and multiple counts.
Resolution-preserving resampling techniques from hexagonal to square pixels
were investigated to provide distortion-free display of acquired images.
Results: At 10 cycles/mm, the modulation factor was 0.49. The 2-D NPS did
not show off-axis noise source and the structural noise component was near
zero over all spatial frequencies. The DQE did not exhibit exposure rate
dependence and reached a maximum of approximately 0.85 at midfrequencies (4-5 cycles/mm). For resampling to Cartesian grid, evaluation of
the aperture functions indicated that the 53・m square pixel best matched the
hexagonal pixel (less than 2% deviation at all frequencies). After resampling to
53・m square pixels using Delaunay triangulation based linear interpolation, the
presampling MTF at Nyquist frequency (9.43-cycles/mm) was 0.45.
Conclusion: Hexagonal pixel array photon-counting CdTe detector provides
high spatial resolution and high DQE at fluoroscopic exposure rates. This could
allow for artifact-free subtraction angiography and basis material
decomposition at substantially reduced radiation dose.
13
Microwave ablation zone variance: Identifying which
parameters should be detected and incorporated in patient
specific planning
New potential for employing radiotherapy biomaterials
loaded with anti-CTLA-4 antibody to induce abscopal effect
Garron Deshazer, Punit Prakash, Mark Hagmann, Derek Merck PhD, Damian
Dupuy M.D.
Yao Hao, Gizem Cifter, Yucel Altundal, Neeharika Sinha, Michele Moreau,
Erno Sajo, Mike Makrigiorgos, Wilfred Ngwa
Purpose: Image-guided percutaneous ablation is an, effective, inexpensive,
and accessible treatment for liver, lung, and kidney cancers. However, its
relatively high recurrence rate makes it more palliative. We hypothesize that
higher rates are due in part to inadequate margin estimation, resulting from
over-simplified geometric planning. Better predictive planning is needed,
however, this requires numerical model accounting for the physical
characteristics of heterogeneous tissues around the target. Literature suggests
that pathologies such as cirrhosis and malignant tissue have varying thermal
and electrical properties when compared to normal tissue. The objective of this
study is to employ a simulation based approach to determine the impact of
heterogeneous tissue physical properties on treatment outcome.
Purpose: Studies show that stereotactic body radiation therapy (SBRT) of a
primary tumor in combination with immune checkpoint inhibitors (ICI) could
result in an immune-mediated regression of metastasis outside the radiation
field, a phenomenon known as abscopal effect. However toxicities due to
repeated systematic administration of ICI have been shown to be a major
obstacle in clinical trials. Towards overcoming these toxicity limitations, we
investigate a potential new approach whereby the ICI are administered via
sustained in-situ release from radiotherapy (RT) biomaterials (e.g. fiducials)
coated with a polymer
Methods: An electromagnetic-thermal finite-element model of the BSD Medical
ST antenna was created. The antenna placed inside the center of a tumor that
was immersed within liver tissue. The variance of ablation zone sizes with
tissue physical properties was evaluated by assigning varying tissue dielectric
and thermal properties to the tumor, consistent with data reported in the
literature. 10-30 % variations in tissue effective electrical conductivity, and
varying perfusion levels for tumor, normal, and cirrhotic liver (3-18 kg/m3/s)
were considered. The CEM43 > 240min threshold was used to estimate
ablation zone extents.
Results: When considering 10-30% differences in electrical conductivity and
relative permittivity between malignant and normal tissue there was less than
4mm and 1mm variations in ablation zone extents observed. Perfusion
variations showed the largest difference when compared to homogeneous
simulation (~ 4.5mm -1.0cm).
Conclusion: The results suggest that dielectric inhomogeneities have limited
impact on predicted ablation zone extents. However, variances in tumor and
normal liver tissue blood perfusion, within the range of clinically measured
values reported in the literature, significantly affects predicted ablation zon
Methods: New design RT biomaterials were prepared by coating commercially
available spacers/fiducials with a biocompatible polymer (PLGA) film containing
fluorescent nanoparticles of size needed to load the ICI. The release of the
nanoparticles was investigated in-vitro. Meanwhile, an experimentally
determined in-vivo nanoparticle diffusion coefficient was employed in analytic
calculations based on Fick’s second law to estimate the time for achieving the
concentrations of ICI in the tumor draining lymph node (TDLN) that are needed
to engender the abscopal effect during SBRT. The ICI investigated here was
anti-CTLA-4 antibody (ipilimumab) at approved FDA concentrations.
Results: Our in-vitro study results showed that RT biomaterials could be
designed to achieve burst release of nanoparticles within one day. Meanwhile,
our calculations indicate that for a 2 to 4 cm tumor it would take 4 to 22 days,
respectively, following burst release, for the required concentration of ICI
nanoparticles to accumulate in the TDLN during SBRT.
Conclusions: Current investigations combining RT and immunotherapy
involve repeated intravenous administration of ICI leading to significant
systemic toxicities. Our preliminary results highlight a potential new approach
for sustained in-situ release of the ICI from new design RT biomaterials. These
results provide impetus for more studies to leverage the powerful abscopal
effect, while minimizing systemic toxicities through the new approach.
14
Potential of using cerium oxide nanoparticles (CONP) for
protecting healthy tissue during Accelerated Partial Breast
Irradiation (APBI)
Madan Mainali, Wilfred Ngwa, Gizem Cifter, Jonathan Celli
Purpose: The purpose of this research is to investigate the feasibility of using
targeted cerium oxide nanoparticles (CONP) during APBI to protect healthy
cells.
Methods: In one approach, CONP are assumed to be incorporated in a
micrometer-thick polymer film on the surface of routinely used mammosite
balloon applicators for sustained in-situ release of the CONP. In case two,
CONPs are administered directly into the lumpectomy cavity. The
concentration of H2O2 produced by ionizing radiation was estimated from
previously published work using short range linear extrapolation. The
assessment of CONPs concentration required to absorb corresponding H2O2
to protect healthy tissue was calculated. Fick’s Second law of diffusion was
employed to determine the initial concentration of CONP needed to achieve the
minimum concentration for radioprotection at distance 1 cm and 2 cm from the
lumpectomy cavity during APBI. The study was carried out for different
nanoparticle sizes.
Results: The initial concentration of CONPs required to get desired
radioprotection concentration at 1 cm and 2 cm after 7 days was found to be
0.4089 mg per Kg and 59.7605 g per Kg respectively for 2 nm size
nanoparticles. Using concentrations of 5 mg per kg of CONP that have been
shown to be used to confer radioprotection (for about 7.97 Gy) in experiments
it was observed that 4.5631, 8.5286, 10.9247, 22.0408, 43.6796 and 65.5618
number of days are required to achieve radioprotection at 1 cm for CONP of
sizes 2 nm, 3.8 nm, 5 nm, 10 nm, 20 nm, 30 nm, respectively.
Conclusion: Our preliminary results show that smaller size (2 nm and 3.8 nm)
CONP would be suitable as radio protectant during APBI because they took a
reasonable number of days, i.e. less than 10 days to reach tissues of 1 cm or 2
cm thickness.
15
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