Conformal Dose Delivery Research Articles

AutoCorNN: An Unsupervised Physics-Aware Deep Learning Model for Geometric Distortion Correction of Brain MRI Images Towards MR-Only Stereotactic Radiosurgery.

Geometric distortions in brain MRI images arising from susceptibility artifacts at air-tissue interfaces pose a significant challenge for high-precision radiation therapy modalities like stereotactic radiosurgery, necessitating sub-millimeter accuracy. To achieve this goal, we developed AutoCorNN, an unsupervised physics-aware deep-learning model for correcting geometric distortions. Two publicly available datasets, the MPI-Leipzig Mind-Brain-Body with 318 subjects, and the Vestibular Schwannoma-SEG dataset, encompassing 242 patients were utilized. AutoCorNN integrates two 2D convolutional encoder-decoder neural networks with the forward physical model of MRI signal generation to predict undistorted MR and field map images from distorted MR input. The network is trained in an unsupervised manner by minimizing the mean absolute error between the measured and estimated k-space data, without requiring ground truth images during training or deployment. The model was evaluated on vestibular schwannoma cases. AutoCorNN achieved a peak signal-to-noise ratio (PSNR) of 41.35 ± 0.02dB, a root mean square error (RMSE) of 0.02 ± 0.003, and a structural similarity index (SSIM) of 0.99 ± 0.02 outperforming uncorrected and B0-mapping correction methods. Geometric distortions of about 1.6mm were observed at the air-tissue interfaces at the air canal and nasal cavity borders. Geometrically, distortion correction increased the target volume from 3.12 ± 0.52cc to 3.84 ± 0.54cc. Dosimetrically, AutoCorNN improved target coverage (0.96 ± 0.01 to 0.97 ± 0.02), conformity index (0.92 ± 0.03 to 0.94 ± 0.03), and reduced dose gradients outside the target. AutoCorNN achieves accurate geometric distortion correction comparable to conventional iterative methods while offering substantial computational acceleration, enabling precise target delineation and conformal dose delivery for improved radiation therapy outcomes.

Alanine dosimeters for LET measurement in proton radiotherapy

Proton radiotherapy enables highly conformal dose delivery to the tumor while minimizing exposure to healthy tissues surrounding the target. However, to achieve the most optimal treatment plan, it is necessary to consider various parameters, including variable relative biological effectiveness (RBE) and linear energy transfer (LET) within the target and in the normal tissues. The proton treatment planning systems (TPS) currently under development incorporate both of these parameters. However, before introducing biologically guided treatment planning into the clinic, commissioning and end-to-end tests must be conducted. These procedures require specific tools to verify the planned LET distribution. The same tools will also be necessary for subsequent patient-specific quality assurance (QA).The objective of this work was to evaluate the alanine/EPR dosimetry system developed at the Cyclotron Center Bronowice at the Institute of Nuclear Physics (CCB IFJ PAN) for verifying LET values in therapeutic proton fields. The change in the shape of the EPR spectra of alanine irradiated in proton fields of different LETs, described by the ratio of the intensities of the satellite and central lines (x/y ratio), was used to discriminate LET values. The method does not provide absolute LET values. However, as demonstrated, it can verify the LET values calculated in the TPS after calibration using Monte Carlo (MC) simulation.

A Method for <i>In Vivo</i> Dosimetry Using an Electronic Portal Imaging Device

The implementation of advanced radiotherapy techniques such as Intensity-Modulated RadiationTherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) allows much more accuratecontrol of the irradiation area and more conformal dose delivery. Since these treatments are characterizedby high dose gradients and hence small error margins, they also require advanced and highlyeffective treatment verification techniques. Fortunately, an imaging modality, originally intended forset-up verifications, called the Electronic Portal Imaging Device (EPID) was reported to have hugepotential for dosimetry and treatment verification applications. However, methods and algorithmspreviously developed for EPID dosimetry are not yet widely adopted in cancer centers due to complexitiesin the implementation. These motivate more investigation and development of new methodsto encourage cancer centers to practice EPID dosimetry and improve patient safety.This research generally aims to develop an in-vivo dosimetry method that can be used in the future toapproximate the actual dose delivered inside the target by utilizing the transmitted fluence detectedby the EPID. In this study, Monte Carlo simulations are carried out using the Geant4 Application forTomographic Emission (GATE) to implement a virtual set-up composed of a water target irradiatedwith a monoenergetic 2 MeV photon beam and an EPID model to detect the total transmitted fluence.A mathematical model has been proposed to calculate the target absorbed dose by utilizing the transmittedprimary fluence. This involves back-projection of the transmitted fluence to determine fluencevalues at certain depths inside the irradiated homogeneous medium. This is followed by the calculationof the collision kerma using the back-projected fluence and the values of the linear attenuation coefficientand mass energy absorption coefficient in the National Institute of Standards and Technology(NIST) database. The results show accurate prediction of the fluence values inside the target, calculationof the corresponding values of the collision kerma, and determination of the proportionalityconstant β that relates the collision kerma to the target absorbed dose.

A new Multi Leaf Collimator for the fission neutron therapy facility at FRM II

As a part of the general upgrade program of the fission neutron therapy facility MEDAPP at the research reactor FRM II, a newly designed, electronically operated Multi Leaf Collimator (MLC) was introduced. The design of the new collimator was optimized in order to increase dose output and to allow patient positioning closer to the collimator. The new collimator allows divergent and convergent beam shaping in order to maximize the effective area of the fission source used for irradiation. In comparison to the old MLC, the radiation dose for the staff is reduced by the motorized operation of the new MLC. The advanced beam shaping abilities of the new collimator are investigated by a comparison with depth dose curves and beam profiles of the old MLC. For the separation of neutron and gamma dose deposition in water, the two chamber dosimetry method recommended for mixed field dosimetry was applied. A re-calibration of the set of ionization chambers used for dosimetry in mixed neutron-gamma radiation fields at FRM II was performed. The calibration was done in a reference neutron field from 3H(p,n)3He-reactions in a low scattering environment. An overall increased dose output as intended by the design of the new MLC was shown. Also, improved dosimetric characteristics of the treatment field due to the optimized beam shaping abilities of the new MLC were demonstrated. In the calibration measurements of the magnesium ionization chamber used in the two chamber method, an unexpected increase of the neutron sensitivity by a factor of 8 was measured. The new MLC will enable more conformal dose delivery to the target volume in patients and therefore help to reduce healthy tissue damage by the application of neutron radiation.

Proton beam dosimetry in the presence of magnetic fields using Farmer-type ionization chambers of different radii.

Magnetic resonance-guided proton therapy is promising, as it combines high-contrast imaging of soft tissue with highly conformal dose delivery. However, proton dosimetry in magnetic fields using ionization chambers is challenging since the dose distribution as well as the detector response are perturbed. This work investigates the effect of the magnetic field on the ionization chamber response, and on the polarity and ion recombination correction factors, which are essential for the implementation of a proton beam dosimetry protocol in the presence of magnetic fields. Three Farmer-type cylindrical ionization chambers, the 30013 with 3mm inner radius (PTW, Freiburg, Germany) and two custom built chambers "R1" and "R6" with 1 and 6mm inner radii respectively were placed at the center of an experimental electromagnet (Schwarzbeck Mess - Elektronik, Germany) 2cm depth of an in-house developed 3D printed water phantom. The detector response was measured for a 3×10cm2 field of mono-energetic protons 221.05MeV/u for the three chambers, and with an additional proton beam of 157.43MeV/u for the chamber PTW 30013. The magnetic flux density was varied between 0.1 and 1.0Tesla in steps of 0.1Tesla. At both energies, the ionization chamber PTW 30013 showed a non-linear response as a function of the magnetic field strength, with a decrease of the ionization chamber response of up to 0.27%±0.06% (1 SD) at 0.2Tesla, followed by a smaller effect at higher magnetic field strength. For the chamber R1, the response decreased slightly with the magnetic field strength up to 0.45%±0.12% at 1Tesla, and for the chamber R6, the response decreased up to 0.54%±0.13% at 0.1Tesla, followed by a plateau up to 0.3Tesla, and a weaker effect at higher magnetic field strength. The dependence of the polarity and recombination correction factor on the magnetic field was ⩽0.1% for the chamber PTW 30013. The magnetic field has a small but significant effect on the chamber response in the low magnetic field region for the chamber PTW 30013 and for R6, and in the high magnetic field region for the chamber R1. Corrections may be necessary for ionization chamber measurements, depending on both the chamber volume and the magnetic flux density. No significant effect of the magnetic field on the polarity and recombination correction factor was detected in this work for the ionization chamber PTW 30013.

Intensity Modulation in Electron FLASH Radiotherapy

<h3>Purpose/Objective(s)</h3> Combining methods of conformal dose delivery with ultra-high dose rate (UHDR) beams is advantageous for realizing the benefits of the FLASH effect in clinical treatments. We hypothesize that deployment of intensity modulation in passive electron FLASH radiotherapy through treatment plan optimization is feasible. <h3>Materials/Methods</h3> A beam model of an electron FLASH irradiator (delivering ∼300Gy/s at the isocenter) in the decimal ElectronRT treatment planning system (TPS) was validated with film measured lateral and percent-depth-dose (PDD) profiles. Plans were developed comparing collimated open fields and intensity modulated electron beams achieved with cylindrical passive metal compensators that vary in spacing and size. Homogeneity and conformity were quantified for plans developed in a water phantom and anonymized patient cases considering constraints in prescribed dose to the target volume and minimizing dose to organs-at-risk (OAR). <h3>Results</h3> The film measured profiles and TPS beam model agreed on average to within 1% and 2% for lateral profile and PDD, respectively. For a large 15 × 15 cm² field in a water phantom the intensity modulation improved the beam flatness (∼30% to <5%) and penumbra (35 mm to 15mm) at 3 cm depth while retaining UHDR in the treatment field with a 38% reduction in central axis output while still retaining the UHDR conditions (∼180Gy/sec). The PDD exhibited <2% difference along the central axis and minimal changes to symmetry, shift, and practical range. In the rib metastasis case, the unmodulated and modulated plans treat the tumor volume with a homogeneity index (HI), improvement by 0.2. In the facial orbital plan, the conformity index improved by 8% with an improvement in HI by 0.05 and comparable dose to OARs. <h3>Conclusion</h3> Intensity modulation of electrons FLASH is achievable and improves homogeneity of prescribed dose with proper treatment constraints while reducing hot spots for clinical plans. Depending on the treatment case intensity modulation can also generate superior dose distributions while retaining the UHDR conditions to best exploit the FLASH effect. Future study will focus on demonstrating dosimetric benefits quantified by tumor control probability and normal tissue complication probability models in a larger number of relevant cases.

Low-dose CT allows for accurate proton therapy dose calculation and plan optimization

Objective. Protons offer a more conformal dose delivery compared to photons, yet they are sensitive to anatomical changes over the course of treatment. To minimize range uncertainties due to anatomical variations, a new CT acquisition at every treatment session would be paramount to enable daily dose calculation and subsequent plan adaptation. However, the series of CT scans results in an additional accumulated patient dose. Reducing CT radiation dose and thereby decreasing the potential risk of radiation exposure to patients is desirable, however, lowering the CT dose results in a lower signal-to-noise ratio and therefore in a reduced quality image. We hypothesized that the signal-to-noise ratio provided by conventional CT protocols is higher than needed for proton dose distribution estimation. In this study, we aim to investigate the effect of CT imaging dose reduction on proton therapy dose calculations and plan optimization. Approach. To verify our hypothesis, a CT dose reduction simulation tool has been developed and validated to simulate lower-dose CT scans from an existing standard-dose scan. The simulated lower-dose CTs were then used for proton dose calculation and plan optimization and the results were compared with those of the standard-dose scan. The same strategy was adopted to investigate the effect of CT dose reduction on water equivalent thickness (WET) calculation to quantify CT noise accumulation during integration along the beam. Main results. The similarity between the dose distributions acquired from the low-dose and standard-dose CTs was evaluated by the dose-volume histogram and the 3D Gamma analysis. The results on an anthropomorphic head phantom and three patient cases indicate that CT imaging dose reduction up to 90% does not have a significant effect on proton dose calculation and plan optimization. The relative error was employed to evaluate the similarity between WET maps and was found to be less than 1% after reducing the CT imaging dose by 90%. Significance. The results suggest the possibility of using low-dose CT for proton therapy dose estimation, since the dose distributions acquired from the standard-dose and low-dose CTs are clinically equivalent.

Conformal Dose Modulator for Proton Beam Therapy Part 1: A Simulation Study.

PurposeConformal dose deliveries in proton therapy utilize either a passive scattering system with a modulator or a pencil beam scanning (PBS) system. Efforts have been made to achieve conformal dose delivery by scanning a single energy layer of pencil beams through a 3D conformal modulator (3DCM), which combines a spread-out Bragg peak (SOBP) modulator consisting of a micro-pyramid array and a range compensator. The current published approach of designing such 3DCM relies on forward calculation methods to determine the geometry of the modulator. This study presents an alternative designing algorithm that inversely generates the geometry of a 3DCM paired with a corresponding fluence map, customized to patient-specific clinical indications.MethodsCritical spacing governing the size and separation between neighboring micro-pyramids was first determined, under which the dose homogeneity at desired depths could be achieved. We designed an adaptive ring optimization method using a modified gradient descent algorithm to inversely calculate the geometry of the 3DCM. This method includes several stages that progressively optimize both target coverage and dose conformity. The output contains the geometry of the 3DCM and its corresponding proton fluence map. Monte Carlo (MC) simulation was used to validate the results.ResultsThe critical size and spacing of Lucite pyramids was determined to be 0.5 cm for a 184-MeV pristine proton beam. Using MATLAB (R2020a), the inverse designing algorithm generated an optimized 3DCM geometry and a fluence distribution achieving 100% target coverage with the 90% isodose surface and a corresponding conformity index of 1.057 on a spherical target. The resulting geometry was pruned to accommodate the MC simulation software and a currently accessible 3D printing service. The pruned geometry gave 95% target coverage by 90% isodose surface with a conformity index of 1.09 by ray-tracing dose computation. The MC simulation validated the 3DCM with 95% target coverage by 87% isodose surface and a conformity index of 1.12.ConclusionWe have demonstrated the feasibility of using a novel inverse optimization algorithm to generate 3DCM geometry and its corresponding proton beam fluence/intensity map, which could deliver highly conformal dose distribution with pencil beam scanning system using a single energy layer.

High-Dose Rate Interstitial Spine Brachytherapy Using an Intraoperative Mobile Computed Tomography-Guided Surgical Navigation System.

Up to 15% of previously irradiated metastatic spine tumors will progress. Re-irradiation of these tumors poses a significant risk of exceeding the radiation tolerance to the spinal cord. High-dose rate (HDR) brachytherapy is a treatment alternative. To develop a novel HDR spine brachytherapy technique using an intraoperative computed tomography-guided navigation (iCT navigation). Patients with progressive metastatic spine tumors were included in the study. HDR brachytherapy catheters were placed under iCT navigation. CT-based planning with magnetic resonance imaging fusion was performed to ensure conformal dose delivery to the target while sparing normal tissue, including the spinal cord. Patients received single fraction radiation treatment. Five patients with thoracolumbar tumors were treated with HDR brachytherapy. Four patients previously received radiotherapy to the same spinal level. Preimplant plans demonstrated median clinical target volume (CTV) D90 of 116.5% (110.8%-147.7%), V100 of 95.7% (95.5%-99.6%), and Dmax of 8.08 Gy (7.65-9.8 Gy) to the spinal cord/cauda equina. Postimplant plans provided median CTV D90 of 113.8% (93.6%-120.1%), V100 of 95.9% (87%-99%), and Dmax of 9.48 Gy (6.5-10.3 Gy) to cord/cauda equina. Patients who presented with back pain (n=3) noted symptomatic improvement at a median follow-up of 22 d after treatment. Four patients demonstrated local tumor control of spinal metastatic tumor at a median follow-up of 92 d after treatment. One patient demonstrated radiographic evidence of local tumor progression 2.7 mo after treatment. HDR spine brachytherapy with iCT navigation is a promising treatment alternative to induce local tumor control and reduce pain symptoms associated with metastatic spine disease.

Online Magnetic Resonance-Guided Radiotherapy (oMRgRT) for Gynecological Cancers.

Radiation therapy (RT) is increasingly being used in gynecological cancer management. RT delivered with curative or palliative intent can be administered alone or combined with chemotherapy or surgery. Advanced treatment planning and delivery techniques such as intensity-modulated radiation therapy, including volumetric modulated arc therapy, and image-guided adaptive brachytherapy allow for highly conformal radiation dose delivery leading to improved tumor control rates and less treatment toxicity. Quality on-board imaging that provides accurate visualization of target and surrounding organs at risk is a critical feature of these advanced techniques. As soft tissue contrast resolution is superior with magnetic resonance imaging (MRI) compared to other imaging modalities, MRI has been used increasingly to delineate tumor from adjacent soft tissues and organs at risk from initial diagnosis to tumor response evaluation. Gynecological cancers often have poor contrast resolution compared to the surrounding tissues on computed tomography scan, and consequently the benefit of MRI is high. One example is in management of locally advanced cervix cancer where adaptive MRI guidance has been broadly implemented for adaptive brachytherapy. The role of MRI for external beam RT is also steadily increasing. MRI information is being used for treatment planning, predicting, and monitoring position shifts and accounting for tissue deformation and target regression during treatment. The recent clinical introduction of online MRI-guided radiation therapy (oMRgRT) could be the next step in high-precision RT. This technology provides a tool to take full advantage of MRI not only at the time of initial treatment planning but as well as for daily position verification and online plan adaptation. Cervical, endometrial, vaginal, and oligometastatic ovarian cancers are being treated on MRI linear accelerator systems throughout the world. This review summarizes the current state, early experience, ongoing trials, and future directions of oMRgRT in the management of gynecological cancers.

High-dose-rate brachytherapy for prostate cancer: Rationale, current applications, and clinical outcome.

BackgroundHigh‐dose‐rate brachytherapy (HDR BRT) has been enjoying rapid acceptance as a treatment modality offered to selected prostate cancer patients devoid of risk group, employed either in monotherapy setting or combined with external beam radiation therapy (EBRT) and is currently one of the most active clinical research areas.Recent findingsThis review encompasses all the current evidence to support the use of HDR BRT in various clinical scenario and shines light to the HDR BRT rationale, as an ultimately conformal dose delivery method enabling safe dose escalation to the prostate.ConclusionValid long‐term data, both in regard to the oncologic outcomes and toxicity profile, support the current clinical indication spectrum of HDR BRT. At the same time, this serves as solid, rigid ground for emerging therapeutic applications, allowing the technique to remain in the spotlight alongside stereotactic radiosurgery.

Radiation Pneumonitis Following Lung SBRT: The Role of Circumferential Irradiation to the Anatomic Levels of the Proximal Bronchial Tree

Stereotactic body radiation therapy (SBRT) to the lung with dose escalated, hypofractionated treatments can lead to clinically significant lung toxicity in patients including radiation pneumonitis (RP), fistula, and even fatal hemoptysis. Despite adherence to established dosimetric parameters for the lung and proximal bronchial tree (PBT) patients can still develop RP. Prior analysis of our institution’s lung SBRT cohort indicated that high-dose circumferential radiation (HDCR) of the PBT was associated with development of RP. In this study, we sought to determine if the sensitivity of the PBT to HDCR was consistent throughout the structure. A retrospective analysis was conducted for 42 patients who were treated with lung SBRT at one institution between 2010 and 2018. Treatment plans were evaluated for doses delivered to the lung and PBT as well as for presence of circumferential overlap of fractionation relevant isodose lines with the PBT. The isodose lines that defined HDCR were 15, 16, and 18 Gy, which correspond with the PBT D4cc dose limit for 3x18 Gy, 4x12 Gy, and 5x10 Gy fractionation schemes, respectively. The PBT was divided into trachea, primary bronchi, and secondary bronchi to assess if the effect of HDCR varied based on anatomic location. Posttreatment chest imaging and patient charts were evaluated and RP was graded according to the RTOG Toxicity Criteria. This was classified as mild if RTOG grades 0-1 and moderate if RTOG grades 2-3. There were no grades 4-5 toxicity in this group of patients. Statistical analysis was performed using logistic regression. There was a significant association between HDCR of the secondary bronchi and development of RP (OR, 5.0; 95% CI, 1.21-20.6) but no significant association with HDCR of the primary bronchi (OR, 1.38; 95% CI, 0.18-10.8.) There were no patients with HDCR of the trachea. There was no significant association between D4cc (OR, 0.98; 95% CI, 0.90-1.07) or D.03cc (OR, 1.03; 95% CI, 0.99-1.07) to the PBT, mean lung dose (OR, 2.36; 95% CI, 0.67-8.39), lung V5 (OR, 2.2; 95% CI, 0.63-7.66) or lung V20 (OR, 3.07; 95% CI, 0.83-11.4) and grade of RP. This data suggests that circumferential overlap of the secondary bronchi of the PBT with isodose lines corresponding with the D4cc limit plays a role in the development of symptomatic RP. We postulate that this may be due to the smaller diameter of secondary bronchi, which make them more susceptible to luminal stenosis. This should be considered in SBRT treatment planning as conformal dose delivery can result in high doses to a small portion of the airway. Further investigation and validation of these findings with a larger data set is warranted.

POD-DOSI: A dedicated dosimetry system for GammaPod commissioning and quality assurance.

GammaPod, a stereotactic partial breast irradiator allowing highly conformal radiation dose delivery, has its unique mechanical design and treatment planning system (TPS). However, the uniqueness of the system poses challenges regarding initial GammaPod system commissioning and routine quality assurance (QA). In this study, we report POD-DOSI, a dedicated dosimetry system for accurate and efficient commissioning and QA of GammaPod. The POD-DOSI system consists of two subsystems, POD-Scanner and POD-Calculator. The POD-Scanner is an automatic ion-chamber positioning system driven by two translational stepper motors for anterior-posterior, longitudinal, and lateral beam scanning. The stepper motors are controlled by a microcomputer through an in-house-developed graphical user interface, which can be remotely accessed by a laptop via wireless connection. The POD-Calculator is a commissioned GPU-based Monte Carlo dose calculation engine, which calculates dose by transporting particles from phase space constructed for GammaPod. In our institution, the POD-DOSI system was used for GammaPod TPS commissioning and dose verification. The POD-Calculator was further developed as a secondary dose calculation tool performing patient-specific plan QA before each treatment. The POD-DOSI system has been fully evaluated and tested, both mechanically and dosimetrically, and applied successfully to drive the commissioning of our GammaPod system. The POD-Scanner achieved 0.1mm accuracy in ion-chamber positioning tests. The POD-Calculator generated dose profiles matched well with water phantom measurements and TPS calculations to <0.5mm accuracy. For end-to-end test on 56 different treatment plans, in-water point dose measurements by POD-Scanner were within ±2.20% of the doses calculated by POD-Calculator (range: -2.01% to 2.20%, mean: 0.04%, std_dev: 1.10%). Correspondingly, when switching the calculation medium from water to breast tissue, the point doses calculated by the POD-Calculator were within ±1.60% of the point doses calculated by the GammaPOD TPS (range: -1.59% to 1.51%, mean: -0.02%, std_dev: 0.73%). The average three-dimensional gamma passing rate between the GammaPod TPS doses and the POD-Calculator doses was 97.10% under the 2%/1mm gamma criteria. The POD-DOSI system substantially shortened the GammaPod dosimetry commissioning time from weeks to days. The developed POD-DOSI system resolves the challenges and streamlines the process of GammaPod commissioning and QA. It improves the efficiency and accuracy for both GammaPod commissioning and routine patient-specific QA.

Spine radiosurgery in adolescents and young adults: early outcomes and toxicity in patients with metastatic Ewing sarcoma and osteosarcoma.

There are limited data on spine stereotactic radiosurgery (SRS) in treating adolescent and young adult (AYA) patients. SRS has the advantages of highly conformal radiation dose delivery in the upfront and retreatment settings, means for dose intensification, and administration over a limited number of sessions leading to a decreased treatment burden. In this study, the authors report the oncological and toxicity outcomes for AYA patients with metastatic sarcoma treated with spine radiosurgery and provide clinicians a guide for considerations in dose, volume, and fractionation. An institutional review board-approved database of patients treated with SRS in the period from October 2014 through December 2018 was queried. AYA patients, defined by ages 15-29 years, who had been treated with SRS for spine metastases from Ewing sarcoma or osteosarcoma were included in this analysis. Patients with follow-ups shorter than 6 months after SRS were excluded. Local control, overall survival, and toxicity were reported. Seven patients with a total of 11 treated lesions were included in this study. Median patient age was 20.3 years (range 15.1-26.1 years). Three patients had Ewing sarcoma (6 lesions) and 4 patients had osteosarcoma (5 lesions). The median dose delivered was 35 Gy in 5 fractions (range 16-40 Gy, 1-5 fractions). The median follow-up was 11.1 months (range 6.8-26.0 months). Three local failures were observed within the follow-up period. No acute grade 3 or greater toxicity was observed. One patient developed late grade 3 toxicity consisting of radiation enteritis. This patient had previously received radiation to an overlapping volume with conventional fractionation. SRS re-irradiation for this patient was also performed concurrently with chemotherapy administration. No late grade 4 or higher toxicities were observed. No pain flare or vertebral compression fracture was observed. Three patients died within the follow-up period. SRS for spine metastases from Ewing sarcoma and osteosarcoma can be considered as a treatment option in AYA patients and is associated with acceptable toxicity rates. Further studies must be conducted to determine long-term local control and toxicity for this treatment modality.

Dose painting by dynamic irradiation delivery on an image-guided small animal radiotherapy platform.

Using synchronized three-dimensional stage translation and multiangle radiation delivery to improve conformality and homogeneity of radiation delivery to complexly shaped target volumes for precision preclinical radiotherapy. A CT image of a mouse was used to design irradiation plans to target the spinal cord and an orthotopic lung tumour. A dose painting method is proposed that combines heterogeneous two-dimensional area irradiations from multiple beam directions. For each beam direction, a two-dimensional area was defined based on the projection of the target volume. Each area was divided into many single beam Monte Carlo simulations, based on radiochromic film characterization of a 2.4 mm beam of a commercial precision image-guided preclinical irradiation platform. Beam-on time optimization including all simulated beams from multiple beam directions was used to achieve clinically relevant irradiation objects. Dose painting irradiation plans were compared to irradiation plans using a fixed aperture and rotatable variable aperture collimator. Irradiation plans for the proposed dose painting approach achieved good target coverage, similar dose to avoidance structures in comparison with irradiation using a rotatable variable aperture collimator, and considerably less dose to avoidance volumes in comparison with irradiation using a non-rotatable fixed aperture collimator. Required calculations and beam-on times were considerably longer for the dose painting method. It was shown that the proposed dose painting strategy is a valuable extension to increase the versatility of current generation precision preclinical radiotherapy platforms. More conformal and homogeneous dose delivery may be achieved at the cost of increased radiation planning and delivery duration. More advanced radiation planning for image-guided preclinical radiotherapy platforms can improve target dose conformality and homogeneity with the use of optimized dynamic irradiations with synchronized couch translation. The versatility of these platforms can be increased without hardware modifications.

Ionoacoustics for range monitoring of proton therapy

Proton beams exhibit favourable interaction properties for highly conformal tumour dose delivery with better sparing of surrounding healthy tissue and critical structures in comparison to widely established photon beams. However, full clinical exploitation of these advantages is still hampered by treatment uncertainties, particularly related to the stopping position of protons in tissue, determining the so called Bragg peak, where protons release most of their energy. Hence, several approaches are currently investigated to enable an in-vivo, ideally real-time verification of the proton beam range in the patient. While most of the considered techniques aim at exploiting secondary emissions from nuclear interactions, interest is being regained for alternative, cost-effective solutions exploiting acoustic emissions originating from ion interaction in tissue. This contribution will thus address the basics and recent experiments of this so called “ionoacoustics” for pre-clinical and clinical beam energies.

Intensity-modulated radiation therapy of anal squamous cell carcinoma: Relationship between delineation quality and regional recurrence

Background and purposeIntensity-modulated radiation therapy (IMRT) is currently indicated to treat anal squamous cell carcinoma (ASCC). Conformal dose delivery and steep dose gradients may cause marginal misses. We analyzed patterns of locoregional recurrences (LRR) and delineation quality to determine IMRT-specific predictive factors. Material and methodsLymph node area delineation was classified as “compliant” or “non-compliant” according to experts’ workgroup recommendations. The recurrence volume (Vrecur) was delineated on initial planning-CT by recurrence imaging registration. The Vrecur was determined to be “in-field” (IF), “marginal” (ML), or “out-of-field” (OF) in regard to the 95% isodose coverage. ResultsOut of 165 patients, 30 had LRR. Among the 27 local recurrences (LR), 20 (74%) were IF, 4 (15%) ML, and 2 (7%) OF. Fourteen patients had regional recurrence (RR), amounted to 33 separate recurrence sites (RS). RS were mostly localized in inguinal (n = 12;36,4%), external iliac (n = 7;21.1%), presacral (n = 4;12.1%) and common iliac (n = 3;9.1%) nodes. Eighteen (54.5%) RS were IF, 6 (18.2%) ML, and 9 (27.3%) OF. Performance status ≥2 (p = 0.007) and active smoking (p = 0.025) were predictors of LR. Immunodepression (p = 0.012), external iliac involvement (p < 0.001), and non-compliant delineation for ≥10 areas (p = 0.005) were predictors of RR. ConclusionsNew predictive factors for recurrences of ASSC treated with IMRT have been found, suggesting that the delineation accuracy is essential for regional control.

Image-Guided Multi-Channel Cylinder Brachytherapy for Gynecologic Cancers Involving the Vagina: Initial Experience with Vaginal Dose-Volume Parameters

Image-guided high-dose-rate multichannel vaginal cylinder (MCVC) brachytherapy (BT) permits conformal dose delivery to a vaginal tumor while sparing surrounding organs-at-risk. Due to the proximity of the peripheral channels to the tumor and cylinder surface, the adjacent vaginal mucosa is a dose-limiting structure when using MCVC, however, specific dose-volume limitations are not well characterized. We explored vaginal dose-volume parameters in a series of consecutive patients treated with MCVC for gynecologic cancers involving the vagina.

Radiobiological Optimization in Lung Stereotactic Body Radiation Therapy: Are We Ready to Apply Radiobiological Models?

Lung tumors are often associated with a poor prognosis although different schedules and treatment modalities have been extensively tested in the clinical practice. The complexity of this disease and the use of combined therapeutic approaches have been investigated and the use of high dose-rates is emerging as effective strategy. Technological improvements of clinical linear accelerators allow combining high dose-rate and a more conformal dose delivery with accurate imaging modalities pre- and during therapy. This paper aims at reporting the state of the art and future direction in the use of radiobiological models and radiobiological-based optimizations in the clinical practice for the treatment of lung cancer. To address this issue, a search was carried out on PubMed database to identify potential papers reporting tumor control probability and normal tissue complication probability for lung tumors. Full articles were retrieved when the abstract was considered relevant, and only papers published in English language were considered. The bibliographies of retrieved papers were also searched and relevant articles included. At the state of the art, dose–response relationships have been reported in literature for local tumor control and survival in stage III non-small cell lung cancer. Due to the lack of published radiobiological models for SBRT, several authors used dose constraints and models derived for conventional fractionation schemes. Recently, several radiobiological models and parameters for SBRT have been published and could be used in prospective trials although external validations are recommended to improve the robustness of model predictive capability. Moreover, radiobiological-based functions have been used within treatment planning systems for plan optimization but the advantages of using this strategy in the clinical practice are still under discussion. Future research should be directed toward combined regimens, in order to potentially improve both local tumor control and survival. Indeed, accurate knowledge of the relevant parameters describing tumor biology and normal tissue response is mandatory to correctly address this issue. In this context, the role of medical physicists and the AAPM in the development of radiobiological models is crucial for the progress of developing specific tool for radiobiological-based optimization treatment planning.

Multi-institutional MicroCT image comparison of image-guided small animal irradiators

To recommend imaging protocols and establish tolerance levels for microCT image quality assurance (QA) performed on conformal image-guided small animal irradiators. A fully automated QA software SAPA (small animal phantom analyzer) for image analysis of the commercial Shelley micro-CT MCTP 610 phantom was developed, in which quantitative analyses of CT number linearity, signal-to-noise ratio (SNR), uniformity and noise, geometric accuracy, spatial resolution by means of modulation transfer function (MTF), and CT contrast were performed. Phantom microCT scans from eleven institutions acquired with four image-guided small animal irradiator units (including the commercial PXi X-RAD SmART and Xstrahl SARRP systems) with varying parameters used for routine small animal imaging were analyzed. Multi-institutional data sets were compared using SAPA, based on which tolerance levels for each QA test were established and imaging protocols for QA were recommended. By analyzing microCT data from 11 institutions, we established image QA tolerance levels for all image quality tests. CT number linearity set to R2 > 0.990 was acceptable in microCT data acquired at all but three institutions. Acceptable SNR > 36 and noise levels <55 HU were obtained at five of the eleven institutions, where failing scans were acquired with current-exposure time of less than 120 mAs. Acceptable spatial resolution (>1.5 lp mm−1 for MTF = 0.2) was obtained at all but four institutions due to their large image voxel size used (>0.275 mm). Ten of the eleven institutions passed the set QA tolerance for geometric accuracy (<1.5%) and nine of the eleven institutions passed the QA tolerance for contrast (>2000 HU for 30 mgI ml−1). We recommend performing imaging QA with 70 kVp, 1.5 mA, 120 s imaging time, 0.20 mm voxel size, and a frame rate of 5 fps for the PXi X-RAD SmART. For the Xstrahl SARRP, we recommend using 60 kVp, 1.0 mA, 240 s imaging time, 0.20 mm voxel size, and 6 fps. These imaging protocols should result in high quality images that pass the set tolerance levels on all systems. Average SAPA computation time for complete QA analysis for a 0.20 mm voxel, 400 slice Shelley phantom microCT data set was less than 20 s. We present image quality assurance recommendations for image-guided small animal radiotherapy systems that can aid researchers in maintaining high image quality, allowing for spatially precise conformal dose delivery to small animals.