Feasibility of determining external beam radiotherapy dose using LuSy dosimeter.

INTRODUCTION: Radiation dose measurement is an essential part of radiotherapy to verify the correct delivery of doses to patients and ensure patient safety. Recent advancements in radiotherapy technology have highlighted the need for fast and precise dosimeters. Technologies like FLASH radiotherapy and magnetic-resonance linear accelerators (MR-LINAC) demand dosimeters that can meet their unique requirements. One promising solution is the plastic scintillator-based dosimeter with high spatial resolution and real-time dose output. This study explores the feasibility of using the LuSy dosimeter, an in-house developed plastic scintillator dosimeter for dose verification across various radiotherapy techniques, including conformal radiotherapy (CRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and stereotactic radiosurgery (SRS). MATERIALS AND METHODS: A new dosimetry system, comprising a new plastic scintillator as the sensing material, was developed and characterized for radiotherapy beams. Treatment plans were created for conformal radiotherapy, IMRT, VMAT, and SRS and delivered to a phantom. LuSy dosimeter was used to measure the delivered dose for each plan on the surface of the phantom and inside the target volumes. Then, LuSy measurements were compared against an ionization chamber, MOSFET dosimeter, radiochromic films, and dose calculated using the treatment planning system (TPS). RESULTS: For CRT, surface dose measurement by LuSy dosimeter showed a deviation of -5.5% and -5.4% for breast and abdomen treatment from the TPS, respectively. When measuring inside the target volume for IMRT, VMAT, and SRS, the LuSy dosimeter produced a mean deviation of -3.0% from the TPS. Surface dose measurement resulted in higher TPS discrepancies where the deviations for IMRT, VMAT, and SRS were -2.0%, -19.5%, and 16.1%, respectively. CONCLUSION: The LuSy dosimeter was feasible for measuring radiotherapy doses for various treatment techniques. Treatment delivery verification enables early error detection, allowing for safe treatment delivery for radiotherapy patients.

Secondary neutron dosimetry for conformal FLASH proton therapy.

BACKGROUND: Cyclotron-based proton therapy systems utilize the highest proton energies to achieve an ultra-high dose rate (UHDR) for FLASH radiotherapy. The deep-penetrating range associated with this high energy can be modulated by inserting a uniform plate of proton-stopping material, known as a range shifter, in the beam path at the nozzle to bring the Bragg peak within the target while ensuring high proton transport efficiency for UHDR. Aluminum has been recently proposed as a range shifter material mainly due to its high compactness and its mechanical properties. A possible drawback lies in the fact that aluminum has a larger cross-section of producing secondary neutrons compared to conventional plastic range shifters. Accordingly, an increase in secondary neutron contamination was expected during the delivery of range-modulated FLASH proton therapy, potentially heightening neutron-induced carcinogenic risks to the patient. PURPOSE: We conducted neutron dosimetry using simulations and measurements to evaluate excess dose due to neutron exposure during UHDR proton irradiation with aluminum range shifters compared to plastic range shifters. METHODS: Monte Carlo simulations in TOPAS were performed to investigate the secondary neutron production characteristics with aluminum range shifter during 225 MeV single-spot proton irradiation. The computational results were validated against measurements with a pair of ionization chambers in an out-of-field region ( ≤ $\le$ 30 cm) and with a Proton Recoil Scintillator-Los Alamos rem meter in a far-out-of-field region (0.5-2.5 m). The assessments were repeated with solid water slabs as a surrogate for the conventional range shifter material to evaluate the impact of aluminum on neutron yield. The results were compared with the International Electrotechnical Commission (IEC) standards to evaluate the clinical acceptance of the secondary neutron yield. RESULTS: For a range modulation up to 26 cm in water, the maximum simulated and measured values of out-of-field secondary neutron dose equivalent per therapeutic dose with aluminum range shifter were found to be ( 0.57 ± 0.02 ) mSv/Gy $(0.57\pm 0.02)\ \text{mSv/Gy}$ and ( 0.46 ± 0.04 ) mSv/Gy $(0.46\pm 0.04)\ \text{mSv/Gy}$ , respectively, overall higher than the solid water cases (simulation: ( 0.332 ± 0.003 ) mSv/Gy $(0.332\pm 0.003)\ \text{mSv/Gy}$ ; measurement: ( 0.33 ± 0.03 ) mSv/Gy $(0.33\pm 0.03)\ \text{mSv/Gy}$ ). The maximum far out-of-field secondary neutron dose equivalent was found to be ( 8.8 ± 0.5 $8.8 \pm 0.5$ )  µ Sv / Gy $\umu {\rm Sv/Gy}$ and ( 1.62 ± 0.02 $1.62 \pm 0.02$ )  µ Sv / Gy $\umu {\rm Sv/Gy}$ for the simulations and rem meter measurements, respectively, also higher than the solid water counterparts (simulation: ( 3.3 ± 0.3 $3.3 \pm 0.3$ )  µ Sv / Gy $\umu {\rm Sv/Gy}$ ; measurement: ( 0.63 ± 0.03 $0.63 \pm 0.03$ )  µ Sv / Gy $\umu {\rm Sv/Gy}$ ). CONCLUSIONS: We conducted simulations and measurements of secondary neutron production under proton irradiation at FLASH energy with range shifters. We found that the secondary neutron yield increased when using aluminum range shifters compared to conventional materials while remaining well below the non-primary radiation limit constrained by the IEC regulations.

Analysis of a novel X-ray lens for converging beam radiotherapy.

We describe the development and analysis of a new teletherapy modality that, through a novel approach to targeted radiation delivery, has the potential to provide greater conformality than conventional photon-based treatments. The proposed system uses an X-ray lens to reflect photons from a conventional X-ray tube toward a focal spot. The resulting dose distributions have a highly localized peak dose, with lower doses in the converging radiation cone. Physical principles governing the design of this system are presented, along with a series of measurements analyzing various characteristics of the converging beam. The beam was designed to be nearly monoenergetic (~ 59 keV), with an energy bandwidth of approximately 10 keV allowing for treatment energies lower than conventional therapies. The focal spot was measured to be approximately 2.5 cm long and 4 mm wide. Mounting the proposed X-ray delivery system on a robotic arm would allow sub-millimeter accuracy in focal spot positioning, resulting in highly conformal dose distribution via the optimal placement of individual focal spots within the target volume. Aspects of this novel radiation beam are discussed considering their possible clinical application as a treatment approach that takes maximum advantage of the unique properties afforded by converging X-ray beam therapy.

Towards real-time PGS range monitoring in proton therapy of prostate cancer.

Proton therapy of prostate cancer (PCPT) was linked with increased levels of gastrointestinal toxicity in its early use compared to intensity-modulated radiation therapy (IMRT). The higher radiation dose to the rectum by proton beams is mainly due to anatomical variations. Here, we demonstrate an approach to monitor rectal radiation exposure in PCPT based on prompt gamma spectroscopy (PGS). Endorectal balloons (ERBs) are used to stabilize prostate movement during radiotherapy. These ERBs are usually filled with water. However, other water solutions containing elements with higher atomic numbers, such as silicon, may enable the use of PGS to monitor the radiation exposure of the rectum. Protons hitting silicon atoms emit prompt gamma rays with a specific energy of 1.78 MeV, which can be used to monitor whether the ERB is being hit. In a binary approach, we search the silicon energy peaks for every irradiated prostate region. We demonstrate this technique for both single-spot irradiation and real treatment plans. Real-time feedback based on the ERB being hit column-wise is feasible and would allow clinicians to decide whether to adapt or continue treatment. This technique may be extended to other cancer types and organs at risk, such as the oesophagus.

Evaluating the Reproducibility of Mouse Anatomy under Rotation in a Custom Immobilization Device for Conformal FLASH Radiotherapy.

The observation of an enhanced therapeutic index for FLASH radiotherapy in mice has created interest in practical laboratory-based FLASH irradiators. To date, systems capable of 3D conformal FLASH irradiation in mice have been lacking. We are developing such a system, incorporating a high-current linear accelerator to produce a collimated X-ray beam in a stationary beamline design, rotating the mouse about a longitudinal axis to achieve conformal irradiation from multiple beam directions. The purpose of this work was to evaluate the reproducibility of mouse anatomy under rotation at speeds compatible with conformal FLASH delivery. Three short-hair mice and two hairless mice were immobilized under anesthesia in body weight-specific contoured plastic molds, and subjected to three rotational (up to 3 revolutions/s) and two non-rotational movement interventions. MicroCT images were acquired before and after each intervention. The displacements of 11 anatomic landmarks were measured on the image pairs. The displacement of the anatomical landmarks with any of the interventions was 0.5 mm or less for 92.4% of measurements, with a single measurement out of 275 (11 landmarks × 5 interventions × 5 mice) reaching 1 mm. There was no significant difference in the displacements associated with rotation compared to those associated with moving the immobilized mouse in and out of a scanner or with leaving the mouse in place for 5 min with no motion. There were no significant differences in displacements between mice with or without hair, although the analysis is limited by small numbers, or between different anatomic landmarks. These results show that anatomic reproducibility under rotation speed corresponding to FLASH irradiation times appears to be compatible with conformal/stereotactic irradiation in mice.

Efficacy of a hydrogel spacer in three-dimensional conformal radiation therapy for prostate cancer.

OBJECTIVES: We aimed to compare the dose constraints fulfillment rate of the three-dimensional conformal radiotherapy treatment plan before and after a hydrogel spacer insertion. METHODS: The planning computed tomography scans of 39 patients who received stereotactic body radiotherapy for prostate cancer were used. All patients inserted a hydrogel spacer and underwent computed tomography scans before and after spacer insertion. The three-dimensional conformal radiotherapy plans according to NCCN classification, low-, intermediate- and high-risk, were made for each patient. Clinical target volume included prostate and seminal vesicle 2 cm for high risk, prostate and seminal vesicle 1 cm for intermediate risk and prostate only for low risk. Three-dimensional conformal radiotherapy including a seven-field conformal technique with 76 Gy in 38 fractions. Dose constraints for rectum and bladder were V70 Gy ≤ 15%, V65 Gy ≤ 30% and V40 Gy ≤ 60%. RESULTS: Among 39 patients, 35 (90%), 19 (49%) and 13 (33%) and 38 (97%), 38 (97%) and 34 (87%) patients before and after the spacer insertion fulfilled rectum dose constraints for low-, intermediate- and high-risk plans, respectively. A hydrogel spacer significantly reduced rectum dose and improved the rectum dose constraints fulfillment rate in intermediate (P < 0.01) and high (P < 0.01), but no difference was found in low-risk plan (P = 0.25). On multivariate analysis, spacer use was associated with the higher rectum dose constraints fulfillment rate. CONCLUSIONS: A hydrogel spacer reduced rectum dose and improved the dose constraints fulfillment rate in three-dimensional conformal radiotherapy plan. Although IMRT is the standard treatment, 3D-CRT using a hydrogel spacer may be a treatment option.

Investigation of elastomeric materials for bolus using stereolithography printing technology in radiotherapy.

PURPOSE: An investigation was conducted of an elastomeric material, VisiJet M2 (3D systems, USA) for use as 3D bolus within high energy photon beams for radiotherapy. Personalized conformal bolus material on complex structures like the nose can be challenging. This material was evaluated for its clinical feasibility due to its pliability and comfort compared to alternatives. METHOD: Regular slabs of bolus were created of various thicknesses for dosimetric and non-dosimetric characterization. Verification culminated with the creation of a custom nose bolus for an end to end verification using an anthropomorphic head phantom. In vivo dosimetry using Gafchromic EBT3 (Ashland, USA) film validated delivered doses from a 6 MV conformal field and a pair of 6 MV volumetric modulated arc therapy (VMAT) beams. RESULTS & CONCLUSION: Non-dosimetric and dosimetric tests were conducted to assess clinical suitability. The bolus was precisely created using stereolithographic (SLA) methods and presented a compliant and uniform water equivalent material with elastic memory. Measurement yielded a physical density of 1.10 g cm-3 and 1.06 relative to water electron density, and the bolus to skin distance was measured to be a maximum of 3 mm. A maximum measured dose difference of <2% was observed for dynamic treatment. Based on the investigation conducted, and the benefits presented for patient comfort while being uniform and water equivalent, and correctly represented within the treatment planning system (TPS), this material has the potential for clinical use for patient specific custom bolus.

In Vivo Bioluminescence Tomography Center of Mass-Guided Conformal Irradiation.

PURPOSE: The cone-beam computed tomography (CBCT)-guided small animal radiation research platform (SARRP) has provided unique opportunities to test radiobiologic hypotheses. However, CBCT is less adept to localize soft tissue targets growing in a low imaging contrast environment. Three-dimensional bioluminescence tomography (BLT) provides strong image contrast and thus offers an attractive solution. We introduced a novel and efficient BLT-guided conformal radiation therapy and demonstrated it in an orthotopic glioblastoma (GBM) model. METHODS AND MATERIALS: A multispectral BLT system was integrated with SARRP for radiation therapy (RT) guidance. GBM growth curve was first established by contrast CBCT/magnetic resonance imaging (MRI) to derive equivalent sphere as approximated gross target volume (aGTV). For BLT, mice were subject to multispectral bioluminescence imaging, followed by SARRP CBCT imaging and optical reconstruction. The CBCT image was acquired to generate anatomic mesh for the reconstruction and RT planning. To ensure high accuracy of the BLT-reconstructed center of mass (CoM) for target localization, we optimized the optical absorption coefficients µa by minimizing the distance between the CoMs of BLT reconstruction and contrast CBCT/MRI-delineated GBM volume. The aGTV combined with the uncertainties of BLT CoM localization and target volume determination was used to generate estimated target volume (ETV). For conformal irradiation procedure, the GBM was first localized by the predetermined ETV centered at BLT-reconstructed CoM, followed by SARRP radiation. The irradiation accuracy was qualitatively confirmed by pathologic staining. RESULTS: Deviation between CoMs of BLT reconstruction and contrast CBCT/MRI-imaged GBM is approximately 1 mm. Our derived ETV centered at BLT-reconstructed CoM covers >95% of the tumor volume. Using the second-week GBM as an example, the ETV-based BLT-guided irradiation can cover 95.4% ± 4.7% tumor volume at prescribed dose. The pathologic staining demonstrated the BLT-guided irradiated area overlapped well with the GBM location. CONCLUSIONS: The BLT-guided RT enables 3-dimensional conformal radiation for important orthotopic tumor models, which provides investigators a new preclinical research capability.

The influence of errors in small field dosimetry on the dosimetric accuracy of treatment plans.

Background: Dosimetric effects of inaccuracies of output factors (OFs) implemented in treatment planning systems (TPSs) were investigated.Materials and methods: Modified beam models (MBM) for which the OFs of small fields (down to 1 × 1 cm2) were increased by up to 12% compared to the original beam models (OBM) were created for two TPSs. These beam models were used to recalculate treatment plans of different complexity. Treatment plans using stereotactic 3D-conformal (s3D-CRT) for brain metastasis as well as VMAT plans for head and neck and prostate cancer patients were generated. Dose distributions calculated with the MBM and the OBM were compared to measured dose distributions acquired using film dosimetry and a 2D-detector-array. For the s3D-CRT plans the calculated and measured dose at the isocenter was evaluated. For VMAT, gamma pass rates (GPRs) were calculated using global gamma index with 3%/3 mm, 2%/3 mm, 1%/3 mm and 2%/2 mm with a 20% threshold. Contribution of small fields to the total fluence was expressed as the ratio (F) of fluence trough leaf openings smaller than 2 cm to the total fluence.Results: Using film dosimetry for the s3D-CRT plans, the average of the ratio of calculated dose to measured dose at the isocenter was 1.01 and 1.06 for the OBM and MBM model, respectively. A significantly lower GPR of the MBM compared to the OBM was only found for the localized prostate cases (F = 12.4%) measured with the 2D-detector-array and an acceptance criterion of 1%/3 mm.Conclusion: The effects of uncertainties in small field OFs implemented in TPSs are most pronounced for s3D-CRT cases and can be clearly identified using patient specific quality assurance. For VMAT these effects mainly remain undetected using standard patient specific quality assurance. Using tighter acceptance criteria combined with an analysis of the fluence generated by small fields can help identifying inaccuracies of OFs implemented in TPSs.

Monte Carlo simulation of a 2D dynamic multileaf collimator to improve the plan quality in radiotherapy plan: a proof-of-concept study.

The leaf width of a multileaf collimator (MLC) determines the dose conformity to the target volume. The objective of this study was to investigate the feasibility of a two-dimensional dynamic MLC (2DDMLC) to improve the treatment plan quality with a fixed leaf width. The treatment head of the Clinac™ linear accelerator with the Millennium 120™ MLC was modelled with the Geant4 (for GEometry ANd Tracking) tollkit using the Monte Carlo (MC) method. The 2DDMLC produces a beam aperture by moving the MLC bank vertically to the leaf movement. Thus, the effect of the 2DDMLC motion on beam divergence and beam fluence resolution was evaluated by comparing the dose distributions between the conventional MLC motion and the 2DDMLC. Finally, the 2DDMLC was employed for dynamic conformal arc therapy for 13 brain cancer patients. The dose-volumetric parameters, including the dose delivered to 98% of the target volume (D 98%), percent volume given 20% of the prescribed dose (V 20%), and conformity index (CI) were compared with those of the conventional MLC. For the 6 MV beam of the MC model, the depth dose and lateral dose distribution differed by less than 2% between the simulation and measurement. The 2DDMLC did not significantly influence beam divergence and sharpened the beam. In clinical use, the dose delivered to the target was almost identical between the 2DDMLC and conventional MLC (D 98% = 29.74 Gy versus 29.71 Gy, p  = 0.18). The CI was improved with the use of the 2DDMLC (CI = 1.49 versus 1.47, p  = 0.14). Moreover, irradiation of normal tissue was reduced with the 2DDMLC compared with conventional MLC (V 20% = 17.22% versus 17.45%, p  < 0.001). The 2DDMLC improved the dose conformity to the target volume and reduced the irradiation of the normal tissue compared with the conventional MLC.

In Vivo Three-Dimensional Two-Photon Microscopy to Study Conducted Vascular Responses by Local ATP Ejection Using a Glass Micro-Pipette.

Maintenance of normal brain function requires a sufficient and efficient supply of oxygen and nutrition by a complex network of vessels. However, the regulation of cerebral blood flow (CBF) is incompletely understood, especially at the capillary level. Two-photon microscopy is a powerful tool widely used to study CBF and its regulation. Currently, this field is limited by the lack of in vivo two-photon microscopy studies examining (1) CBF responses in three-dimensions, (2) conducted vascular responses, and (3) localized interventions within the vascular network. Here, we describe a 3D in vivo method using two-photon microscopy to study conducted vascular responses elicited by local ejection of ATP with a glass micro-pipette. Our method uses fast and repetitive hyperstack two-photon imaging providing precise diameter measurements by maximal intensity projection of the obtained images. Furthermore, we show that this method can also be used to study 3D astrocytic calcium responses. We also discuss the advantages and limitations of glass micro-pipette insertion and two-photon hyperstack imaging.

Eliminating Daily Shifts, Tattoos, and Skin Marks: Streamlining Isocenter Localization With Treatment Plan Embedded Couch Values for External Beam Radiation Therapy.

PURPOSE: The Radiation Oncology Incident Learning System demonstrated that incorrect or omitted patient shifts during treatment are common near-misses or incidents. This single pediatric hospital quality improvement experience evaluated a markless isocenter localization workflow to improve safety and streamline treatment, obviating the need for daily shifts. METHODS AND MATERIALS: Patients undergoing radiation therapy were simulated and treated with indexed immobilization devices. User origins were established at simulation based on a limited set of fixed couch-top references. In treatment planning, shifts from the user origin to the planned isocenter were converted to absolute couch parameters and embedded in the setup field parameters. Thus, the first fraction did not require any shifts. Before kilovoltage imaging, setup verification was often supplemented with surface-guided imaging. After image guidance and final couch adjustments, couch parameters could be reacquired and used for subsequent treatments. No skin marks were used. RESULTS: Over 3 years, approximately 300 patients were treated with over 5000 treatment fractions using this workflow. There were no wrong-site treatment errors. Approximately a dozen near-miss events related to the daily setup process occurred, largely on the first treatment. Root-cause analysis attributed errors to user origin misidentification, couch parameter miscalculation, incorrect immobilization device use, and immobilization device indexed at the wrong indexing position. Skin marks and tattoos were unnecessary. Continuous quality improvement added additional quality assurance checks, resulting in no near-miss incidents or adverse events in the preceding 12 months. CONCLUSION: We minimized near-miss incidents by using limited simulation user origins, converting user origin-to-isocenter shifts to absolute couch parameters, and enforcing restrictive tolerance tables to limit delivery parameter changes, coupled with surface guidance and quality assurance tools. This technique can be applied across institutions, age ranges, and tumor types and with or without surface guidance. This workflow has removed a common treatment setup error and the need for skin marks.

Stereotactic radiotherapy for choroidal melanomas by means of HybridArc™ : Physics and technique of linac-based photon beam therapy.

PURPOSE: Stereotactic radiotherapy (SRT) is suitable to treat ocular tumours. The optimal beam geometry for SRT, however, has not been defined. Here we evaluate a combination technique with dynamic conformal arcs (DCAs) and intensity-modulated static fields (IMRT), known as HybridArc™ (HA). METHODS: For the first consecutive 25 cases with choroidal melanomas with volumes of 0.02 to 1.18 cm3 treated with 50 Gy in five fractions, the results with respect to dose conformity, homogeneity, and dose distributions were summarised. To describe the dose distribution at the planning target volume (PTV) boundary, we defined a spatially averaged dose gradient (SADG) and compared it with Paddick's gradient index (GI). We made dosimetric comparisons between HA and other irradiation techniques. RESULTS: The PTVs ranged from 0.42 to 3.37 cm3. The conformity index (CI) was 1.25 ± 0.15, and the homogeneity index (HI) 0.08 ± 0.02. The SADG was (-3.5 ± 0.5) Gy/mm or (-7.0 ± 1.0) %/mm between the isodose levels 95 and 20%; local minima reached -11.5 Gy/mm or -22.9%/mm. The coefficient of determination for a nonlinear regression of GI on SADG was 0.072. After a median follow-up time of 19.6 months, local tumour control was 100% without any case of post-therapeutic enucleation. Two patients (8%) developed liver metastases. CONCLUSION: SRT of ocular tumours by HA is highly appropriate, and HA is superior to intensity-modulated arc therapy (IMAT) concerning dose reduction in organs at risk (OARs). The novel gradient measure SADG is more informative than Paddick's GI.

Equipment, staffing, and provision of radiotherapy in Lombardy, Italy: Results of three surveys performed between 2012 and 2016.

INTRODUCTION:: Several efforts are being implemented at the European level to measure provision of up-to-date radiation treatments across the continent. METHODS:: A snapshot survey involving all radiation oncology centers within Lombardy, Italy, was performed in 2012 and repeated in 2014 and 2016, in cooperation with regional governmental officers. Centers were asked to provide detailed information concerning all individual patients being treated on the index day, and to report data on available local resources. RESULTS:: We observed an increase in the number of centers and of megavoltage units (MVU) (from 76 to 87, i.e., 8.7 MVU per million inhabitants in 2016). Mean number of MVU per center was 2.5. Average age of MVU increased from 5.3 to 7.5 years and patients on the waiting list also increased. Conformal 3D radiotherapy (RT) treatments decreased from 56% to 42% and were progressively replaced by intensity-modulated RT treatments (from 39% to 49%). Waiting times were overall satisfactory. Radiation oncologists treated on average 152 and radiation therapists 100 RT courses per year. Average reimbursement per course was €4,879 (range €2,476-€8,014). CONCLUSIONS:: The methodology of snapshot survey proved feasible and provided valuable information about radiation oncology provision and accessibility in Lombardy.

Integration of radiobiological modeling and indices in comparative plan evaluation: A study comparing VMAT and 3D-CRT in patients with NSCLC.

PURPOSE: The purpose of this article was to generate an algorithm to calculate radiobiological endpoints and composite indices and use them to compare volumetric modulated arc therapy (VMAT) and 3-dimensional conformal radiation therapy (3D-CRT) techniques in patients with locally advanced non-small cell lung cancer. METHODS AND MATERIALS: The study included 25 patients with locally advanced non-small cell lung cancer treated with 3D-CRT at our center between January 1, 2010, and December 31, 2014. The planner generated VMAT plans using clones of the original computed tomography scans and regions of interest volumes, which did not include the original 3D plans. Both 3D-CRT and VMAT plans were generated using the same dose-volume constraint worksheet. The dose-volume histogram parameters for planning target volume and relevant organs at risk (OAR) were reviewed. The calculation engine was written in the R programming language; the user interface was developed with the "shiny" R Web library. Dose-volume histogram data were imported into the calculation engine and tumor control probability (TCP), normal tissue complication probability (NTCP), composite cardiopulmonary toxicity index (CPTI), morbidity index: MI = ∑j = 1#ofrelevantOARs(wj ∗ NTCPj), uncomplicated TCP (UTCP=TCP∗∏k=1#ofOARs1-NTCPK100, and therapeutic gain (TG): ie, TG = TCP ∗ (100 - MI) were calculated. RESULTS: TCP was better with 3D-CRT (12.62% vs 11.71%, P < .001), whereas VMAT demonstrated superior NTCP esophagus (4.45% vs 7.39%, P = .02). NTCP spinal cord (0.001% vs 0.009%, P = .001), and NTCP heart/perfusion defect (44.57% vs 56.42%, P = .016). There was no difference in NTCP lung (6.27% vs 7.62%, P = .221) and NTCP heart/pericarditis (0.001% vs 0.15%, P = .129) between 2 techniques. VMAT showed substantial improvement in morbidity index (11.06% vs. 14.31%, P = 0.01), CPTI (47.59% vs 59.41%, P = .03), TG (P = .035), and trend toward superiority in UTCP (5.89 vs 4.75, P=.057). CONCLUSION: The study highlights the utility of the radiobiological algorithm and summary indices in comparative plan evaluation and demonstrates benefits of VMAT over 3D-CRT.

Quality control methods for linear accelerator radiation and mechanical axes alignment.

PURPOSE: The delivery accuracy of highly conformal dose distributions generated using intensity modulation and collimator, gantry, and couch degrees of freedom is directly affected by the quality of the alignment between the radiation beam and the mechanical axes of a linear accelerator. For this purpose, quality control (QC) guidelines recommend a tolerance of ±1 mm for the coincidence of the radiation and mechanical isocenters. Traditional QC methods for assessment of radiation and mechanical axes alignment (based on pointer alignment) are time consuming and complex tasks that provide limited accuracy. In this work, an automated test suite based on an analytical model of the linear accelerator motions was developed to streamline the QC of radiation and mechanical axes alignment. METHODS: The proposed method used the automated analysis of megavoltage images of two simple task-specific phantoms acquired at different linear accelerator settings to determine the coincidence of the radiation and mechanical isocenters. The sensitivity and accuracy of the test suite were validated by introducing actual misalignments on a linear accelerator between the radiation axis and the mechanical axes using both beam steering and mechanical adjustments of the gantry and couch. RESULTS: The validation demonstrated that the new QC method can detect sub-millimeter misalignment between the radiation axis and the three mechanical axes of rotation. A displacement of the radiation source of 0.2 mm using beam steering parameters was easily detectable with the proposed collimator rotation axis test. Mechanical misalignments of the gantry and couch rotation axes of the same magnitude (0.2 mm) were also detectable using the new gantry and couch rotation axis tests. For the couch rotation axis, the phantom and test design allow detection of both translational and tilt misalignments with the radiation beam axis. For the collimator rotation axis, the test can isolate the misalignment between the beam radiation axis and the mechanical collimator rotation axis from the impact of field size asymmetry. The test suite can be performed in a reasonable time (30-35 min) due to simple phantom setup, prescription-based beam delivery, and automated image analysis. As well, it provides a clear description of the relationship between axes. After testing the sensitivity of the test suite to beam steering and mechanical errors, the results of the test suite were used to reduce the misalignment errors of the linac to less than 0.7-mm radius for all axes. CONCLUSIONS: The proposed test suite offers sub-millimeter assessment of the coincidence of the radiation and mechanical isocenters and the test automation reduces complexity with improved efficiency. The test suite results can be used to optimize the linear accelerator's radiation to mechanical isocenter alignment by beam steering and mechanical adjustment of gantry and couch.

COMP report: CPQR technical quality control guideline for medical linear accelerators and multileaf collimators.

The Canadian Organization of Medical Physicists (COMP), in close partnership with the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series of Technical Quality Control (TQC) guidelines for radiation treatment equipment. These guidelines outline the performance objectives that equipment should meet in order to ensure an acceptable level of radiation treatment quality. The TQC guidelines have been rigorously reviewed and field tested in a variety of Canadian radiation treatment facilities. The development process enables rapid review and update to keep the guidelines current with changes in technology (the most updated version of this guideline can be found on the CPQR website). This particular TQC details recommended quality control testing for medical linear accelerators and multileaf collimators.

Análisis de impacto presupuestal de radioterapia para el tratamiento de cánceres del sistema urinario en Colombia / Budget impact analysis of radiotherapy for the treatment of cancers of the urinary system in Colombia

INTRODUCCIÓN: El análisis de impacto presupuestal (AIP) de radioterapia para el tratamiento de cánceres del sistema urinario en Colombia, se desarrolló en el marco del mecanismo técnicocientífico para la ampliación progresiva del Plan de Beneficios en Salud con cargo a la UPC (PBSUPC) y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. Los carcinomas uroteliales (CU) son los cuartos tumores más comunes (1). Pueden ubicarse en las vías urinarias inferiores (vejiga y uretra) o superiores (cavidades pialeocíclicas y uréter). Los tumores de la vejiga representan el 90-95% de los CU y son la malignidad más común de las vías urinarias. En las estimaciones reportadas por Globocan 2012, sólo están disponibles los datos epidemiológicos para el cáncer de riñón y cáncer de vejiga. La tasa de incidencia ajustada por edad a nivel mundial en ambos sexos para el cáncer de riñón es de 2,4 por 100.000 habitantes y para cáncer de vejiga de 3,1 por 100.000 (4). La tasa de mortalidad para el cáncer de riñón es del 1,7 por 100.000 y para el cáncer de vejiga del 2,0 por 100.000 habitantes. En Colombia, de acuerdo a las estimaciones realizadas por el Instituto Nacional de Cancerología (INC) para el periodo de 2007 a 2011, la tasa de incidencia ajustada por edad de cáncer de riñón coincide con la reportada por GLOBOCAN 2012, y la tasa de incidencia ajustada por edad de cáncer de vejiga es ligeramente mayor en los hombres colombianos (3,9 por 100.000 habitantes). En las mujeres, las tasas de incidencia ajustadas por edad para el cáncer de vejiga y cáncer de riñón son menores en comparación con los hombres (TAE de 1,2 por 100.000 para cáncer de vejiga y TAE de 1,9 por 100.000 para cáncer de riñón). La radioterapia tiene un impacto en el control locorregional y en la supervivencia global y por causa específica en muchos tumores primarios; sin embargo, su uso ha implicado un riesgo real de efectos secundarios agudos y crónicos que potencialmente pueden, en casos seleccionados, traducirse en una morbi-mortalidad importante y/o reducir la calidad de vida de los pacientes. Actualmente en el plan de beneficios del Sistema General de Seguridad Social en Salud (SGSSS) en Colombia, únicamente la radioterapia Conformacional 3D (3D CRT) está indicada para el manejo del cáncer gástrico; sin embargo, su uso también es requerido en cánceres del sistema urinario como cáncer de la pelvis renal, vejiga y uréteres. El objetivo del presente AIP es estimar el esfuerzo financiero necesario para la adopción de la radioterapia 3D CRT en el tratamiento de los cánceres del sistema urinario, en un horizonte temporal de tres años. TECNOLOGÍAS EVALUADAS: Tratamiento actual: Para la realización del presente documento se ha considerado que a pesar de que la radioterapia convencional 2D aún se encuentra incluida en el Plan de Beneficios en Salud con cargo a la UPC (PBSUPC), su capacidad técnica no es comparable con la radioterapia conformada tridimensional (3D CRT) para el tratamiento del cáncer de vejiga, cáncer de la pelvis renal y cáncer de uréteres, por tanto no existe una tecnología de radioterapia comparable en el sistema de salud colombiano. Tanto las guías de práctica internacionales como las sociedades científicas incluyen dentro de sus recomendaciones la radioterapia 3D CRT para el manejo de las neoplasias. El concepto de radioterapia 3D CRT, que contempla tratamientos con intención radical, incremento de dosis postoperatoria y volúmenes críticos a órganos cercanos, entre otras, ha sucedido a las planificaciones realizadas hasta ahora en solo dos dimensiones del espacio (2D). El concepto de radioterapia 3D CRT, que contempla tratamientos con intención radical, incremento de dosis postoperatoria y volúmenes críticos a órganos cercanos, entre otras, ha sucedido a las planificaciones realizadas hasta ahora en solo dos dimensiones del espacio (2D). considerando antecedentes irrefutables de la radioterapia, que en general propende por dosis más altas de irradiación para incrementar el control loco-regional de la enfermedad, que se traduce a su vez en aumentos de la supervivencia y dosis más altas de irradiación disminuyendo la incidencia de efectos secundarios a largo plazo. En Colombia, el INC, referente nacional para el manejo del cáncer y sus complicaciones, ha excluido la radioterapia convencional 2D de sus protocolos, y ha emitido las recomendaciones específicas para radioterapia de Intensidad Modulada (IMRT) y la radioterapia 3D CRT. De acuerdo a los lineamientos de manejo del INC, los cánceres del sistema urinario deben manejarse con radioterapia 3D CRT. En este sentido, se considera el uso de radioterapia convencional 2D como práctica de tratamiento para casos de Urgencias oncológicas de Radioterapia y como radioterapia neoadyuvante hasta dosis límite permitida con el compromiso de remisión de ese paciente a las instituciones que ofrezcan tecnología avanzada como 3D CRT e IMRT para que complete el tratamiento del paciente. Teniendo en cuenta que el PBSUPC incluye la radioterapia convencional 2D, para efectos del análisis de impacto presupuestal se incluye la radioterapia 2D como tratamiento actual, a pesar de las consideraciones expresadas previamente. TECNOLOGÍA EVALUADA: De acuerdo a la consulta de expertos y revisión de guías de práctica clínica, en la actualidad se utiliza la radioterapia 3D CRT para el tratamiento de los cánceres del sistema urinario como el cáncer de vejiga, cáncer de la pelvis renal y cáncer de uréteres. Sin embargo, en el PBSUPC está tecnología no está indicada para este tipo de cánceres. Considerando este escenario, la tecnología a evaluar será la radioterapia 3D CRT. INSUMOS Y MÉTODOS: Esta sección presenta los supuestos, parámetros y métodos utilizados para el modelo de estimación del impacto presupuestal describiendo la siguiente información: Perspectiva: Se abordó la perspectiva del tercer pagador el cual corresponde al Sistema General de Seguridad Social en Salud (SGSSS). Horizonte temporal: El horizonte temporal utilizado corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión de la radioterapia 3D CRT en la financiación con recursos públicos asignados a la salud en el año 1. Población total: Corresponde a la población de todas las edades, reportada en la Base de Datos Única de Afiliados (BDUA) de 2016. A partir de esta población se estimó la población objetivo, por medio de tasas de incidencia de los diferentes tipos de cánceres del sistema urinario. Modelo: Se desarrolló un modelo de impacto presupuestal, donde dada la distribución de mercado actual y la indicación de radioterapia para los cánceres del sistema urinario, se plantean dos escenarios con una cobertura total de la nueva tecnología. Los impactos vienen acompañados de análisis de sensibilidad univariados. Resultados: Dado que la tecnología de la radioterapia 3D CRT corresponde al tratamiento nuevo y es el manejo estándar actual según expertos clínicos, se planteó una cobertura del 100% para los dos escenarios incluidos.

Análisis de impacto presupuestal de radioterapia para el tratamiento de cánceres del sistema gastrointestinal en Colombia / Budget impact analysis of radiotherapy for the treatment of cancers of the gastrointestinal system in Colombia

INTRODUCCIÓN: El análisis de impacto presupuestal (AIP) de radioterapia para el tratamiento de cánceres del sistema gastrointestinal en Colombia se desarrolló en el marco del mecanismo técnicocientífico para la ampliación progresiva del Plan de Beneficios en Salud con cargo a la UPC (PBSUPC) y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. El cáncer gastrointestinal (CGI) es un término para el grupo de cánceres que afectan el sistema digestivo. A nivel mundial, representa el 20% de los nuevos casos estimados de cáncer y el 15% de las muertes estimadas. Este término incluye cánceres de esófago, vesícula biliar, hígado, páncreas, estómago, intestino delgado, intestino grueso o colon y recto, y ano. La radioterapia tiene un papel importante en el manejo de estas diversas neoplasias malignas, incluyendo su uso como terapia adyuvante antes o después de la cirugía, como radiación definitiva con o sin quimioterapia, y como paliación de síntomas locales o enfermedad lejana. De acuerdo a Globocan 2012, los cánceres del sistema digestivo que presentan una mayor incidencia a nivel mundial en ambos sexos son el cáncer colorrectal (CCR) (TEA 17,2 por 100.000 habitantes), el cáncer gástrico (TEA 12,1 por 100.000) y el cáncer de hígado (TEA 10,1 por 100.000). Respecto a la mortalidad, los CGI asociados a una mayor tasa de mortalidad son el cáncer de hígado (TEA 9,1 por 100.000), cáncer gástrico (TEA 8,8 por 100.000) y el cáncer colorectal (TEA 8,5 por 100.000). En Colombia, el cáncer gástrico corresponde a la primera causa de muerte por cáncer en ambos sexos a pesar de la marcada disminución en las tasas de mortalidad por cáncer gástrico durante los últimos 30 años (de una TEA de 21 en hombres y de 13,9 en mujeres por 100.000 habitantes en 1984-88, a 14,7 en hombres y 8,2 en mujeres por 100.00 habitantes en 2008. En el año 2012 se diagnosticaron 5.663 pacientes con CCR en Colombia, con una incidencia de 7,6 por 100.000 para los hombres y de 7,0 por 100.000 para las mujeres. Respecto a los otros CGI, el Instituto Nacional de Cancerología (INC) en el periodo de 2007 a 2011 estimó las siguientes incidencias anuales en hombres y mujeres respectivamente, por cada 100.000 habitantes: cáncer de esófago de 3,0 y 1,3; cáncer de hígado de 2,8 y 2,6; cáncer de páncreas de 2,6 y 3,0; y cáncer de vesícula biliar de 1,4 y 3,6. La radioterapia tiene un impacto en el control locorregional y en la supervivencia global y por causa específica en muchos tumores primarios; sin embargo, su uso ha implicado un riesgo real de efectos secundarios agudos y crónicos que potencialmente pueden, en casos seleccionados, traducirse en una morbi-mortalidad importante y/o reducir la calidad de vida de los pacientes. Actualmente en el plan de beneficios del Sistema General de Seguridad Social en Salud (SGSSS) en Colombia, únicamente la radioterapia Conformacional 3D (3D CRT) está indicada para el manejo del cáncer gástrico, a pesar de su utilidad reconocida para el manejo de otros cánceres del sistema digestivo. De acuerdo a expertos clínicos, además de la radioterapia 3D CRT, la radioterapia de intensidad modulada (IMRT, del inglés intensity-modulated radiation therapy) es una tecnología que se ha venido usando en los últimos años en ciertos tipos de cáncer debido a su menor toxicidad e incluso ha llegado a convertirse en la práctica estándar del tratamiento radioterápico en algunas instituciones. sin embargo, esta tecnología de alto costo aún no se encuentra incluida en el plan de beneficios en salud. El objetivo del presente Análisis de Impacto Presupuestal (AIP) es estimar el esfuerzo financiero necesario para la adopción de la radioterapia 3D CRT o IMRT en el tratamiento de los cánceres del sistema gastrointestinal, en un horizonte temporal de tres años. TECNOLOGÍAS EVALUADAS: Para la realización del presente documento se ha considerado que a pesar de que la radioterapia convencional 2D aún se encuentra incluida en el PBSUPC, su capacidad técnica no es comparable con la radioterapia 3D CRT o IMRT para el tratamiento de los canceres gastrointestinales. Tanto las guías de práctica internacionales como las sociedades científicas incluyen dentro de sus recomendaciones tecnologías tales como la radioterapia 3D CRT y la radioterapia IMRT, e incluso nuevas alternativas con mayores desarrollos científicos, para el manejo de las neoplasias. El concepto de radioterapia 3D CRT, que contempla tratamientos con intención radical, escalonamiento de dosis, incremento de dosis postoperatoria, disminución de dosis en los órganos a riesgo y de los volúmenes críticos a órganos cercanos entre otras, ha sucedido a las planificaciones realizadas hasta ahora en solo dos dimensiones del espacio (2D). donde tanto el volumen blanco como los órganos vecinos nobles recibían la misma dosis alta, ocasionando efectos deletéreos; esto sumado a la consideración de los antecedentes irrefutables de la radioterapia, que en general propende por dosis más altas de irradiación al volumen blanco para conseguir el efecto antineoplásico curativo incrementando el control loco-regional de la enfermedad, que se traduce a su vez en aumentos de la supervivencia y disminución de la incidencia de efectos secundarios a largo plazo. En Colombia, el INC, referente nacional para el manejo del cáncer y sus complicaciones, ha excluido la radioterapia convencional 2D de sus protocolos, y ha emitido las recomendaciones específicas para radioterapia con IMRT, siendo considerada la radioterapia 3D CRT el estándar de manejo y reemplazado por IMRT solo en los casos indicados. En este sentido, se considera el uso de radioterapia convencional 2D como práctica de tratamiento para casos de Urgencias oncológicas de Radioterapia y como radioterapia neoadyuvante hasta dosis límite permitida con el compromiso de remisión de ese paciente a las instituciones que ofrezcan tecnología avanzada como 3D CRT e IMRT para que complete el tratamiento del paciente. Teniendo en cuenta que el PBSUPC incluye la radioterapia convencional 2D, para efectos del análisis de impacto presupuestal se incluye la radioterapia 2D como tratamiento actual, a pesar de las consideraciones expresadas previamente. De acuerdo a la consulta de expertos, en la práctica clínica se utiliza la radioterapia 3D CRT o la radioterapia IMRT para el tratamiento de diferentes CGI, según la disponibilidad de los equipos en las instituciones y de indicaciones específicas. Sin embargo, dichas tecnologías aún no se encuentran incluidas en el PBSUPC para el tratamiento de cánceres específicos como el cáncer de esófago, cáncer gastroesofágico, cáncer gástrico (se requiere la técnica IMRT en casos especiales), cáncer de páncreas y/o vías biliares, cáncer de hígado, cáncer anal y cáncer rectal. Considerando dicho escenario, las tecnologías a evaluar serán la radioterapia 3D CRT y la IMRT. INSUMOS Y MÉTODOS: Esta sección presenta los supuestos, parámetros y métodos utilizados para el modelo de estimación del impacto presupuestal describiendo la siguiente información: Perspectiva: Se abordó la perspectiva del Sistema General de Seguridad Social en Salud (SGSSS). Horizonte temporal: El horizonte temporal utilizado corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión de la radioterapia IMRT y 3D CRT en la financiación con recursos públicos asignados a la salud en el año 1. Población total: Corresponde a la población de todas las edades, asumiendo una cobertura universal en la información suministrada por la Base de Datos Única de Afiliados (BDUA). A partir de esta población se estimó la población objetivo, por medio de tasas de incidencia de los diferentes tipos de CGI. RESULTADOS: Los resultados que se presentan a continuación, detallan el escenario actual del tratamiento de la enfermedad (escenario 1, primer año), frente a dos escenarios hipotéticos que por concepto de los desarrolladores, pueden presentarse para los siguientes años de análisis. Para el año 3 del escenario 1 y para el escenario 2 se planteó el uso de las radioterapias 3D CRT e IMRT de acuerdo con las indicaciones clínicas para cada tipo de cáncer gastrointestinal específico.

Treating locally advanced lung cancer with a 1.5T MR-Linac - Effects of the magnetic field and irradiation geometry on conventionally fractionated and isotoxic dose-escalated radiotherapy.

PURPOSE: This study investigates the feasibility and potential benefits of radiotherapy with a 1.5T MR-Linac for locally advanced non-small cell lung cancer (LA NSCLC) patients. MATERIAL AND METHODS: Ten patients with LA NSCLC were retrospectively re-planned six times: three treatment plans were created according to a protocol for conventionally fractionated radiotherapy and three treatment plans following guidelines for isotoxic target dose escalation. In each case, two plans were designed for the MR-Linac, either with standard (∼7mm) or reduced (∼3mm) planning target volume (PTV) margins, while one conventional linac plan was created with standard margins. Treatment plan quality was evaluated using dose-volume metrics or by quantifying dose escalation potential. RESULTS: All generated treatment plans fulfilled their respective planning constraints. For conventionally fractionated treatments, MR-Linac plans with standard margins had slightly increased skin dose when compared to conventional linac plans. Using reduced margins alleviated this issue and decreased exposure of several other organs-at-risk (OAR). Reduced margins also enabled increased isotoxic target dose escalation. CONCLUSION: It is feasible to generate treatment plans for LA NSCLC patients on a 1.5T MR-Linac. Margin reduction, facilitated by an envisioned MRI-guided workflow, enables increased OAR sparing and isotoxic target dose escalation for the respective treatment approaches.