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At least 973 records · Page 54
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DOE OSTI2015

SU-E-P-25: Evaluation of Motion in Pancreas SBRT Treatment Deliveries

Purpose: Stereotactic Body Radiation Therapy (SBRT) procedures for pancreatic cancer present a challenge in motion management because the target is directly adjacent to critical structures and the target is subject to significant respiratory motion. Gated treatment is usually planned with a tight (few mm) PTV margin. The positioning and setup relies on on-board-imaging (OBI) of internal fiducials. This study evaluates the corrections for inter- and intra-fractional target motion as evidenced by the OBI. Methods: 20 patients with gated pancreas SBRT treatment were setup with KV imaging guidance before and during each treatment. The couch position was fine-tuned to align with the internal fiducials for each patient. The data for 148 intra- and 111 inter-fractional couch movements were captured and analyzed. Results: The mean ± standard deviation of couch shifts for the initial daily setup is 4.9±4.1 mm for couch vertical, 5.3±4.6 mm for couch longitudinal, and 3.7±4.0 mm for couch lateral. The mean ± standard deviation of intra-treatment adjustments are 1.1±1.6, 2.5±3.8, and 1.1±1.8 mm for couch vertical, longitudinal and lateral. The probability of intra-fractional motion in the three orthogonal directions with magnitude no more than 2 mm, 3 mm and 5 mm is 55%, 68% and 84% respectively. Conclusion: The intra-treatment target motion for pancreas SBRT patients indicates that a PTV margin of 5mm may be necessary.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-T-08: A Beam Source Model for Monte Carlo Simulations of a Double-Scattering Proton Beam Delivery System Using Beam Current Modulation

Purpose: To reconstruct phase-space information upstream of patient specific collimators for Monte Carlo simulations using only radiotherapy planning system data. Methods: The proton energies are calculated based on residual ranges, e.g., sum of prescribed ranges in a patient and SSD. The Kapchinskij and Vladimirskij (KV) distribution was applied to sample proton’s x-y positions and momentum direction and the beam shape was assumed to be a circle. Free parameters, e.g., the initial energy spread and the emittance of KV distribution were estimated from the benchmarking with commissioning data in a commercial treatment planning system for an operational proton therapy center. The number of histories, which defines the height of individual pristine Bragg peaks (BP) of Spread-out Bragg peak (SOBP), are weighted based on beam current modulation and a correction factor is applied to take into account the fluence reduction as the residual range decreases due to the rotation of the range modulator wheel. The timedependent behaviors, e.g., the changes of the residual range and histories per a pristine BP, are realized by utilizing TOPAS (Tool for Particle Simulation). Results: Benchmarking simulations for selected SOBPs ranging 7.5 cm to 15.5 cm matched within 2 mm in range and up to 5 mm in SOBP width against measurement data in water phantom. We found this model tends to underestimate entrance dose by about 5 % in comparison to measurement. This was attributed to the situation that the energy distribution used in the model was limited in its granularity at the limit of single energy spectrum for the narrow angle modulator steps used in the proximal pull back region of the SOBPs. Conclusion: Within these limitations the source modeling method proved itself an acceptable alternative of a full treatment head simulation when the machine geometry and materials information are not available.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-T-133: Assessing IMRT Treatment Delivery Accuracy and Consistency On a Varian TrueBeam Using the SunNuclear PerFraction EPID Dosimetry Software

Purpose: To assess if the TrueBeam HD120 collimator is delivering small IMRT fields accurately and consistently throughout the course of treatment using the SunNuclear PerFraction software. Methods: 7-field IMRT plans for 8 canine patients who passed IMRT QA using SunNuclear Mapcheck DQA were selected for this study. The animals were setup using CBCT image guidance. The EPID fluence maps were captured for each treatment field and each treatment fraction, with the first fraction EPID data serving as the baseline for comparison. The Sun Nuclear PerFraction Software was used to compare the EPID data for subsequent fractions using a Gamma (3%/3mm) pass rate of 90%. To simulate requirements for SRS, the data was reanalyzed using a Gamma (3%/1mm) pass rate of 90%. Low-dose, low- and high gradient thresholds were used to focus the analysis on clinically relevant parts of the dose distribution. Results: Not all fractions could be analyzed, because during some of the treatment courses the DICOM tags in the EPID images intermittently change from CU to US (unspecified), which would indicate a temporary loss of EPID calibration. This technical issue is still being investigated. For the remaining fractions, the vast majority (7/8 of patients, 95% of fractions, and 96.6% of fields) are passing the less stringent Gamma criteria. The more stringent Gamma criteria caused a drop in pass rate (90 % of fractions, 84% of fields). For the patient with the lowest pass rate, wet towel bolus was used. Another patient with low pass rates experienced masseter muscle wasting. Conclusion: EPID dosimetry using the PerFraction software demonstrated that the majority of fields passed a Gamma (3%/3mm) for IMRT treatments delivered with a TrueBeam HD120 MLC. Pass rates dropped for a DTA of 1mm to model SRS tolerances. PerFraction pass rates can flag missing bolus or internal shields. Sanjeev Saini is an employee of Sun Nuclear Corporation. For this study, a pre-release version of PerFRACTION 1.1 software from Sun Nuclear Corporation was used.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-T-638: Proton Beam Delivery to a Moving Lung Tumor and Monte Carlo Simulation with TOPAS

Purpose: To estimate the dose delivered to a moving lung tumor by proton therapy beams of different modulation types, and compare with Monte Carlo predictions. Methods: A radiology support devices (RSD) phantom was irradiated with therapeutic proton radiation beams using two different types of modulation: uniform scanning (US) and double scattered (DS). The Eclipse© dose plan was designed to deliver 1.00Gy to the isocenter of a static ∼3×3×3cm (27cc) tumor in the phantom with 100% coverage. The peak to peak amplitude of tumor motion varied from 0.0 to 2.5cm. The radiation dose was measured with an ion-chamber (CC-13) located within the tumor. The time required to deliver the radiation dose varied from an average of 65s for the DS beams to an average of 95s for the US beams. Results: The amount of radiation dose varied from 100% (both US and DS) to the static tumor down to approximately 92% for the moving tumor. The ratio of US dose to DS dose ranged from approximately 1.01 for the static tumor, down to 0.99 for the 2.5cm moving tumor. A Monte Carlo simulation using TOPAS included a lung tumor with 4.0cm of peak to peak motion. In this simulation, the dose received by the tumor varied by ∼40% as the period of this motion varied from 1s to 4s. Conclusion: The radiation dose deposited to a moving tumor was less than for a static tumor, as expected. At large (2.5cm) amplitudes, the DS proton beams gave a dose closer to the desired dose than the US beams, but equal within experimental uncertainty. TOPAS Monte Carlo simulation can give insight into the moving tumor — dose relationship. This work was supported in part by the Philips corporation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

SU-D-BRA-03: Analysis of Systematic Errors with 2D/3D Image Registration for Target Localization and Treatment Delivery in Stereotactic Radiosurgery

Purpose: Determine systematic deviations between 2D/3D and 3D/3D image registrations with six degrees of freedom (6DOF) for various imaging modalities and registration algorithms on the Varian Edge Linac. Methods: The 6DOF systematic errors were assessed by comparing automated 2D/3D (kV/MV vs. CT) with 3D/3D (CBCT vs. CT) image registrations from different imaging pairs, CT slice thicknesses, couch angles, similarity measures, etc., using a Rando head and a pelvic phantom. The 2D/3D image registration accuracy was evaluated at different treatment sites (intra-cranial and extra-cranial) by statistically analyzing 2D/3D pre-treatment verification against 3D/3D localization of 192 Stereotactic Radiosurgery/Stereotactic Body Radiation Therapy treatment fractions for 88 patients. Results: The systematic errors of 2D/3D image registration using kV-kV, MV-kV and MV-MV image pairs using 0.8 mm slice thickness CT images were within 0.3 mm and 0.3° for translations and rotations with a 95% confidence interval (CI). No significant difference between 2D/3D and 3D/3D image registrations (P>0.05) was observed for target localization at various CT slice thicknesses ranging from 0.8 to 3 mm. Couch angles (30, 45, 60 degree) did not impact the accuracy of 2D/3D image registration. Using pattern intensity with content image filtering was recommended for 2D/3D image registration to achieve the best accuracy. For the patient study, translational error was within 2 mm and rotational error was within 0.6 degrees in terms of 95% CI for 2D/3D image registration. For intra-cranial sites, means and std. deviations of translational errors were −0.2±0.7, 0.04±0.5, 0.1±0.4 mm for LNG, LAT, VRT directions, respectively. For extra-cranial sites, means and std. deviations of translational errors were - 0.04±1, 0.2±1, 0.1±1 mm for LNG, LAT, VRT directions, respectively. 2D/3D image registration uncertainties for intra-cranial and extra-cranial sites were comparable. Conclusion: The Varian Edge radiosurgery 6DOF-based system, can perform 2D/3D image registration with high accuracy for target localization in image-guided stereotactic radiosurgery. The work was supported by a Research Scholar Grant, RSG-15-137-01-CCE from the American Cancer Society.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-J-192: A Quick and Effective Method to Validate Patient’s Daily Setup and Geometry Changes Prior to Proton Treatment Delivery Based On Water Equivalent Thickness Projection Imaging (WETPI) for Head Neck Cancer (HNC) Patient

Purpose: With the implementation of Cone-beam Computed-Tomography (CBCT) in proton treatment, we introduces a quick and effective tool to verify the patient’s daily setup and geometry changes based on the Water-Equivalent-Thickness Projection-Image(WETPI) from individual beam angle. Methods: A bilateral head neck cancer(HNC) patient previously treated via VMAT was used in this study. The patient received 35 daily CBCT during the whole treatment and there is no significant weight change. The CT numbers of daily CBCTs were corrected by mapping the CT numbers from simulation CT via Deformable Image Registration(DIR). IMPT plan was generated using 4-field IMPT robust optimization (3.5% range and 3mm setup uncertainties) with beam angle 60, 135, 300, 225 degree. WETPI within CTV through all beam directions were calculated. 3%/3mm gamma index(GI) were used to provide a quantitative comparison between initial sim-CT and mapped daily CBCT. To simulate an extreme case where human error is involved, a couch bar was manually inserted in front of beam angle 225 degree of one CBCT. WETPI was compared in this scenario. Results: The average of GI passing rate of this patient from different beam angles throughout the treatment course is 91.5 ± 8.6. In the cases with low passing rate, it was found that the difference between shoulder and neck angle as well as the head rest often causes major deviation. This indicates that the most challenge in treating HNC is the setup around neck area. In the extreme case where a couch bar is accidently inserted in the beam line, GI passing rate drops to 52 from 95. Conclusion: WETPI and quantitative gamma analysis give clinicians, therapists and physicists a quick feedback of the patient’s setup accuracy or geometry changes. The tool could effectively avoid some human errors. Furthermore, this tool could be used potentially as an initial signal to trigger plan adaptation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-173: One-Scan Protocol: Verifying the Delivery of Spot-Scanning Proton Beam

Purpose: Radiochromic film for spot-scanning QA provides high spatial resolution and efficiency gains from one-shot irradiation for multiple depths. However, calibration can be a tedious procedure which may limit widespread use. Moreover, since there may be an energy dependence, which manifests as a depth dependence, this may require additional measurements for each patient. We present a one-scan protocol to simplify the procedure. Methods: We performed the calibration using an EBT3 film at depths of 18, 20, 24cm of Plastic Water exposed by a 6-level step-wedge plan on a Proteus Plus proton system (IBA, Belgium). The calibration doses ranged 65–250 cGy(RBE) for proton energies of 170–200MeV. A clinical prostate+nodes plan was used for validation. The planar doses at selected depths were measured with EBT3 films and analyzed using one-scan protocol (one-scan digitization of QA film and at least one film exposed to known dose). The Gamma passing rates, dose-difference maps, and profiles of 2D planar doses measured with EBT3 film, IBA MatriXX PT, versus TPS calculations were analyzed and compared. Results: The EBT3 film measurement results matched well with the TPS calculation data with an average passing rate of ∼95% for 2%/2mm and slightly lower passing rates were obtained from an ion chamber array detector. We were able to demonstrate that the use of a proton step-wedge provided clinically acceptable results and minimized variations between film-scanner orientation, inter-scan, and scanning conditions. Furthermore, it could be derived from no more than two films exposed to known doses (one could be zero) for rescaling the master calibration curve at each depth. Conclusion: The use of a proton step-wedge for calibration of EBT3 film increases efficiency. The sensitivity of the calibration to depth variations has been explored. One-scan protocol results appear to be comparable to that of the ion chamber array detector. One author has a research grant from Ashland Inc., the manufacturer of the GafChromic film.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-233: Evaluation of Treatment Delivery Parameters Using High Resolution ELEKTA Log Files

Purpose: As modern linacs have become more technologically advanced with the implementation of IGRT and IMRT with HDMLCs, a requirement for more elaborate tracking techniques to monitor components’ integrity is paramount. ElektaLog files are generated every 40 milliseconds, which can be analyzed to track subtle changes and provide another aspect of quality assurance. This allows for constant monitoring of fraction consistency in addition to machine reliability. With this in mind, it was the aim of the study to evaluate if ElektaLog files can be utilized for linac consistency QA. Methods: ElektaLogs were reviewed for 16 IMRT patient plans with >16 fractions. Logs were analyzed by creating fluence maps from recorded values of MLC locations, jaw locations, and dose per unit time. Fluence maps were then utilized to calculate a 2D gamma index with a 2%–2mm criteria for each fraction. ElektaLogs were also used to analyze positional errors for MLC leaves and jaws, which were used to compute an overall error for the MLC banks, Y-jaws, and X-jaws by taking the root-meansquare value of the individual recorded errors during treatment. Additionally, beam on time was calculated using the number of ElektaLog file entries within the file. Results: The average 2D gamma for all 16 patient plans was found to be 98.0±2.0%. Recorded gamma index values showed an acceptable correlation between fractions. Average RMS values for MLC leaves and the jaws resulted in a leaf variation of roughly 0.3±0.08 mm and jaw variation of about 0.15±0.04 mm, both of which fall within clinical tolerances. Conclusion: The use of ElektaLog files for day-to-day evaluation of linac integrity and patient QA can be utilized to allow for reliable analysis of system accuracy and performance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-384: Step and Shoot IMRT, VMAT and Autoplan VMAT Nasopharnyx Plan Robustness to Linear Accelerator Delivery Errors

Purpose: To identify the robustness of different treatment techniques in respect to simulated linac errors on the dose distribution to the target volume and organs at risk for step and shoot IMRT (ssIMRT), VMAT and Autoplan generated VMAT nasopharynx plans. Methods: A nasopharynx patient dataset was retrospectively replanned with three different techniques: 7 beam ssIMRT, one arc manual generated VMAT and one arc automatically generated VMAT. Treatment simulated uncertainties: gantry, collimator, MLC field size and MLC shifts, were introduced into these plans at increments of 5,2,1,−1,−2 and −5 (degrees or mm) and recalculated in Pinnacle. The mean and maximum doses were calculated for the high dose PTV, parotids, brainstem, and spinal cord and then compared to the original baseline plan. Results: Simulated gantry angle errors have <1% effect on the PTV, ssIMRT is most sensitive. The small collimator errors (±1 and ±2 degrees) impacted the mean PTV dose by <2% for all techniques, however for the ±5 degree errors mean target varied by up to 7% for the Autoplan VMAT and 10% for the max dose to the spinal cord and brain stem, seen in all techniques. The simulated MLC shifts introduced the largest errors for the Autoplan VMAT, with the larger MLC modulation presumably being the cause. The most critical error observed, was the MLC field size error, where even small errors of 1 mm, caused significant changes to both the PTV and the OAR. The ssIMRT is the least sensitive and the Autoplan the most sensitive, with target errors of up to 20% over and under dosages observed. Conclusion: For a nasopharynx patient the plan robustness observed is highest for the ssIMRT plan and lowest for the Autoplan generated VMAT plan. This could be caused by the more complex MLC modulation seen for the VMAT plans. This project is supported by a grant from NSW Cancer Council.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-387: A Novel Optimization Technique for Field in Field (FIF) Chestwall Radiation Therapy Using a Single Plan to Improve Delivery Safety and Treatment Planning Efficiency

Purpose: A novel optimization technique was developed for field-in-field (FIF) chestwall radiotherapy using bolus every other day. The dosimetry was compared to currently used optimization. Methods: The prior five patients treated at our clinic to the chestwall and supraclavicular nodes with a mono-isocentric four-field arrangement were selected for this study. The prescription was 5040 cGy in 28 fractions, 5 mm bolus every other day on the tangent fields, 6 and/or 10 MV x-rays, and multileaf collimation.Novelly, tangents FIF segments were forward planned optimized based on the composite bolus and non-bolus dose distribution simultaneously. The prescription was spilt into 14 fractions for both bolus and non-bolus tangents. The same segments and monitor units were used for the bolus and non-bolus treatment. The plan was optimized until the desired coverage was achieved, minimized 105% hotspots, and a maximum dose of less than 108%. Each tangential field had less than 5 segments.Comparison plans were generated using FIF optimization with the same dosimetric goals, but using only the non-bolus calculation for FIF optimization. The non-bolus fields were then copied and bolus was applied. The same segments and monitor units were used for the bolus and non-bolus segments. Results: The prescription coverage of the chestwall, as defined by RTOG guidelines, was on average 51.8% for the plans that optimized bolus and non-bolus treatments simultaneous (SB) and 43.8% for the plans optimized to the non-bolus treatments (NB). Chestwall coverage of 90% prescription averaged to 80.4% for SB and 79.6% for NB plans. The volume receiving 105% of the prescription was 1.9% for SB and 0.8% for NB plans on average. Conclusion: Simultaneously optimizing for bolus and non-bolus treatments noticeably improves prescription coverage of the chestwall while maintaining similar hotspots and 90% prescription coverage in comparison to optimizing only to non-bolus treatments.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-502: FFF Beams, Jaw-Tracking and Treatment Techniques: Out of Field Dose Considerations for Pediatric Radiation Therapy Delivery

Purpose: To compare the extended dose profile delivered by 3DCRT and VMAT techniques for flattened and flattening-filter-free(FFF) photon beams (6X, 6XFFF,10XFFF), with and without jaw-tracking (JT) on Varian TrueBeam linac. The goal is to determine which treatment technique/modality will minimize the peripheral photon dose exposure (and ultimately minimize the risk of second malignant neoplasms (SMN)) in pediatric patients. Methods: 3DCRT, VMAT, and jaw tracking VMAT (JTVMAT) plans with 6X, 6XFFF and 10XFFF x-ray beams were created on a 30×60×22.5cm solid water phantom with a 551 cc PTV. The 3DCRT plans consisted of a 4FLD arrangement. The optimization objectives for the single-arc VMAT plans was V95%Rx=98% to PTV and minimize dose to a 5cm diameter organ at risk (OAR). The OAR to PTV distance varied from 0–30cm along the long axis at 7.5cm depth. The dose to the center of the OAR was measured using a 0.6cc ion chamber. Results: Relative to the 6X flattened beam, the 10XFFF photon beam had the lowest dose in the penumbra and peripheral region (>15 cm) region by up to 20% and 40%, respectively for all modalities (3DCRT, VMAT, JTVMAT). The 6XFFF beams only showed a dose reduction in the peripheral region (by up to 20%). JT did not significantly affect the peripheral dose for all modalities and energies. Conclusion: Treating pediatric patients with a 10XFFF beam is the most effective way to reduce photon scatter dose in both the penumbra and peripheral regions. However, the neutron dose contribution resulting from the 10MV beam still needs to be considered. For all modalities, 6XFFF was the next effective method to reduce peripheral photon doses. 3DCRT beams had the lowest peripheral doses for all energies compared to VMAT and JTVMAT, however previous publications have shown that this comes at the expense of PTV conformity and OAR sparing.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-660: Evaluating the Benefit of Using Dual-Function Fiducial Markers for In-Situ Delivery of Radiosenistizing Gold Nanoparticles During Image-Guided Radiotherapy

Purpose: Dual-function fiducials loaded with radiosensitizers, like gold nanoparticles (GNP), offer an innovative approach for ensuring geometric accuracy during image-guided radiotherapy (IGRT) and significantly increasing therapeutic efficacy due to controlled in-situ release of the radiosensitizers. This study retrospectively investigates the dosimetric benefit of using up to two such dual-function fiducial markers instead of traditional single function fiducials during IGRT. Methods: A computational code was developed to investigate the dosimetric benefit for 10 real patient tumor volumes of up to 6.5 cm diameter. The intra-tumoral space-time biodistribution of the GNP was modeled as in previous studies based on Fick’s second law. The corresponding dose-enhancement for each tumor voxel due to the GNP was also calculated for clinical 6MV beam configurations. Various loading concentrations (25–50 mg/g) were studied, as a function of GNP size, to determine potential for clinically significant dose enhancement. The time between initial implantation of dual-function fiducials to the beginning of radiotherapy was assumed to be 14 days as typical for many clinics. Results: A single dual-function fiducial could achieve at least a DEF of 1.2 for patients with tumors less than 1.4 cm diameter after 14 days. Replacing two single function fiducials with dual-function ones at the same locations achieved at least the required minimal DEF for tumors that are 2 cm diameter in 3 patients. The results also revealed dosimetrically better fiducial locations which could enable significant DEF when using one or two dual function fiducials. 2 nm sizes showed the most feasibility. Conclusion: The results highlight the potential of tumor sub-volume radiation boosting using GNP released from fiducials, and the ability to customize the DEF throughout the tumor by using two dual-function fiducials, varying the initial concentration and nanoparticle size. The results demonstrate potential for employing dual-function fiducials in the development of GNP-aided radiotherapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MO-FG-CAMPUS-JeP2-05: MRI-Guided Single-Fraction Boost Delivery On Individual Axillary Lymph Nodes

Purpose: The Utrecht MRI-linac (MRL) design enables new MR-guided radiotherapy (RT) approaches. This is a feasibility study for a single-fraction high dose (boost) to individual lymph nodes (LNs) in breast-cancer patients, after breast-conserving surgery (BCS) and hypofractionated whole-breast irradiation (WBI) with conventional axillary RT (AxRT). Methods: After written informed consent, 5 breast-cancer patients (cT1-3N0) were enrolled (NL500460.041.14 trial) and underwent 1.5T MRI in supine RT position, after BCS. Axillary levels, based on ESTRO guidelines, and organs-at-risk (OARs) – including lungs, chest wall, plexus and neurovascular bundle (NVB) – were delineated. Pseudo-CT scans (pCTs) were generated by HU bulk-assignment of water, lung, and air. With Monaco treatment-planning software (TPS Elekta), VMAT plans were generated for simultaneous WBI and AxRT, prescribing 16×2.66=42.56Gy (V95%>99% V107%<2cc). Two scenarios were considered: AxRT of levels I–II; AxRT of levels I–IV, depending on boost location. Per patient, 4 LNs with varying axillary locations were selected, delineated, and expanded to PTV with 2-mm margin. Using dedicated MRL TPS, accounting for magnetic-field effects, an IMRT 1×8.5Gy boost was simulated for each LN, to achieve a total target dose of 66Gy EQD2 (α/β=3.5Gy). WBI/ART doses and boost doses were added, and evaluated in EQD2. Results: For all scenarios, 1×8.5Gy boosts could be simulated within clinical constraints for a 66Gy total dose, in addition to WBI/AxRT. LN target coverage was excellent (V95%>95%, mean >8.5Gy). Additional dose to OARs was limited. Conclusion: Our study explored the concept of LN boosting using on-line MRI guidance. It is feasible to boost individual axillary LNs – with 2-mm margin – with an additional 1×8.5Gy, in all axillary levels, within clinical constraints. This may lead to more personalized RT approaches for patients with involved LNs and may reduce RT-induced toxicity, or the need for axillary surgery. Other LN boost strategies, including dose escalation, are under investigation.

60 APPLIED LIFE SCIENCES↗