Brachytherapy Seed and Applicator Localization via Iterative Forward Projection Matching Algorithm using Digital X-ray Projections

Interstitial and intracavitary brachytherapy plays an essential role in management of several malignancies. However, the achievable accuracy of brachytherapy treatment for prostate and cervical cancer is limited due to the lack of intraoperative planning and adaptive replanning. A major problem in implementing TRUS-based intraoperative planning is an inability of TRUS to accurately localize individual seed poses (positions and orientations) relative to the prostate volume during or after the implantation. For the locally advanced cervical cancer patient, manual drawing of the source positions on orthogonal films can not localize the full 3D intracavitary brachytherapy (ICB) applicator geometry. A new iterative forward projection matching (IFPM) algorithm can explicitly localize each individual seed/applicator by iteratively matching computed projections of the post-implant patient with the measured projections. This thesis describes adaptation and implementation of a novel IFPM algorithm that addresses hitherto unsolved problems in localization of brachytherapy seeds and applicators. The prototype implementation of 3-parameter point-seed IFPM algorithm was experimentally validated using a set of a few cone-beam CT (CBCT) projections of both the phantom and post-implant patient’s datasets. Geometric uncertainty due to gantry angle inaccuracy was incorporated. After this, IFPM algorithm was extended to 5-parameter elongated line-seed model which automatically reconstructs individual seed orientation as well as position. The accuracy of this algorithm was tested using both the synthetic-measured projections of clinically-realistic Model-6711 125I seed arrangements and measured projections of an in-house precision-machined prostate implant phantom that allows the orientations and locations of up to 100 seeds to be set to known values. The seed reconstruction error for simulation was less than 0.6 mm/3o. For the physical phantom experiments, IFPM absolute accuracy for position, polar angle, and azimuthal angel were (0.78 ± 0.57) mm, (5.8 ± 4.8)o, and (6.8 ± 4.0)o, respectively. It avoids the need to match corresponding seeds in each projection and accommodates incomplete data, overlapping seed clusters, and highly-migrated seeds. IFPM was further generalized from 5-parameter to 6-parameter model which was needed to reconstruct 3D pose of arbitrary-shape applicators. The voxelized 3D model of the applicator was obtained from external complex combinatorial geometric modeling. It is then integrated into the forward projection matching method for computing the 2D projections of the 3D ICB applicators, iteratively. The applicator reconstruction error for simulation was about 0.5 mm/2o. The residual 2D registration error (positional difference) between computed and actual measured applicator images was less than 1 mm for the intrauterine tandem and about 1.5 mm for the bilateral colpostats in each detector plane. By localizing the applicator’s internal structure and the sources, the effect of intra and inter-applicator attenuation can be included in the resultant dose distribution and CBCT metal streaking artifact mitigation. The localization accuracy of better than 1 mm and 6o has the potential to support more accurate Monte Carlo-based or 2D TG-43 dose calculations in clinical practice. It is hoped the clinical implementation of IFPM approach to localize elongated line-seed/applicator for intraoperative brachytherapy planning may have a positive impact on the treatment of prostate and cervical cancers

A Novel and Clinically Useful Dynamic Conformal Arc (DCA)-Based VMAT Planning Technique for Lung SBRT

PURPOSE: Volumetric modulated arc therapy (VMAT) is gaining popularity for stereotactic treatment of lung lesions for medically inoperable patients. Due to multiple beamlets in delivery of highly modulated VMAT plans, there are dose delivery uncertainties associated with small-field dosimetry error and interplay effects with small lesions. We describe and compare a clinically useful dynamic conformal arc (DCA)-based VMAT (d-VMAT) technique for lung SBRT using flattening filter free (FFF) beams to minimize these effects. MATERIALS AND METHODS: Ten solitary early-stage I-II non-small-cell lung cancer (NSCLC) patients were treated with a single dose of 30 Gy using 3-6 non-coplanar VMAT arcs (clinical VMAT) with 6X-FFF beams in our clinic. These clinically treated plans were re-optimized using a novel d-VMAT planning technique. For comparison, d-VMAT plans were recalculated using DCA with user-controlled field aperture shape before VMAT optimization. Identical beam geometry, dose calculation algorithm, grid size, and planning objectives were used. The clinical VMAT and d-VMAT plans were compared via RTOG-0915 protocol compliances for conformity, gradient indices, and dose to organs at risk (OAR). Additionally, treatment delivery efficiency and accuracy were recorded. RESULTS: All plans met RTOG-0915 requirements. Comparing with clinical VMAT, d-VMAT plans gave similar target coverage with better target conformity, tighter radiosurgical dose distribution with lower gradient indices, and dose to OAR. Lower total number of monitor units and small beam modulation factor reduced beam-on time by 1.75 min (P \u3c 0.001), on average (maximum up to 2.52 min). Beam delivery accuracy was improved by 2%, on average (P \u3c 0.05) and maximum up to 6% in some cases for d-VMAT plans. CONCLUSION: This simple d-VMAT technique provided excellent plan quality, reduced intermediate dose-spillage, and dose to OAR while providing faster treatment delivery by significantly reducing beam-on time. This novel treatment planning approach will improve patient compliance along with potentially reducing intrafraction motion error. Moreover, with less MLC modulation through the target, d-VMAT could potentially minimize small-field dosimetry errors and MLC interplay effects. If available, d-VMAT planning approach is recommended for future clinical lung SBRT plan optimization

Gamma Knife Radiosurgery to Four Brainstem Lesions After Whole Brain Radiation Therapy

Our patient was a 58-year-old female with a history of extensive stage small cell lung cancer initially diagnosed in November 2018. She received palliative radiation to the right hip and whole brain in December of 2018 and then received chemotherapy. Unfortunately, in October 2019, the repeat brain magnetic resonance imaging (MRI) showed recurrent lesions and she was referred for Gamma Knife Radiosurgery (GKRS). At the time of the treatment, she was found to have four brainstem lesions as well as a left frontal lobe and a right frontal lobe lesion. She completed GKRS to all six lesions without any neurological complications seen in her short-term follow-up. This case report adds to the growing body of literature showing safety of GKRS for multiple brainstem lesions

Effect of Different Doses of Sulfur on Growth and Yield of Rapeseed (Brassica campestris var. Lumle Tori)

Sulfur plays an important role in the growth and yield of rapeseed plants. A field experiment was conducted in a randomized complete block design with seven levels of sulfur (60 kg/ha, 50 kg/ha, 40 kg/ha, 30 kg/ha, 20 kg/ha, 10 kg/ha, and 0 kg/ha in three replicates) to evaluate the effect of different doses of sulfur on the growth and yield of rapeseed (Brassica campestris var. Lumle Tori) in Khairahani, Chitwan. Plant height, number of branches per plant, number of pods per plant, pod length, grain per pod, pod weight, fresh weight, dry weight, stover weight, harvest index, and grain yield were recorded.  Significant differences were observed in plant height, yield-related traits, and grain yield. The results showed significant differences between the growth and yield-related traits of the different treatments. Plant height and number of branches increased with increasing sulfur dose, reaching a maximum of 60 kg/ha. The maximum number of pods per plant was observed at 20 kg/ha, and the maximum pod length and grain per pod were observed at 60 kg/ha. Grain yield and harvest index were maximum at 20 kg/ha. The results showed that the maximum grain yield could be obtained by applying 20 kg/ha of sulfur. These findings provide valuable guidance for optimizing agricultural practices to meet the increasing global demand for oilseeds

Predicting the Effect of Indirect Cell Kill in the Treatment of Multiple Brain Metastases via Single-Isocenter/Multitarget Volumetric Modulated Arc Therapy Stereotactic Radiosurgery

PURPOSE: Due to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m-bm) when using single-isocenter/multitarget (SIMT) volumetric modulated arc therapy (VMAT) techniques. However, recent clinical outcome studies show high rates of tumor local control for SIMT-VMAT. In addition to direct cell kill (DCK), another possible explanation includes the effects of indirect cell kill (ICK) via devascularization for a single dose of 15 Gy or more and by inducing a radiation immune intratumor response. This study quantifies the role of indirect cell death in dosimetric errors as a function of spatial patient setup uncertainty for stereotactic treatments of multiple lesions. MATERIAL AND METHODS: Nine complex patients with 61 total tumors (2-16 tumors/patient) were planned using SIMT-VMAT with geometry similar to HyperArc with a 10MV-FFF beam (2400 MU/min). Isocenter was placed at the geometric center of all tumors. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02–11.5) and 1.9 cc (0.11–18.8) with an average distance to isocenter of 5.4 cm (2.2–8.9). The prescription was 20 Gy to each PTV. Plans were recalculated with induced clinically observable patient setup errors [±2 mm, ±2o] in all six directions. Boolean structures were generated to calculate the effect of DCK via 20 Gy isodose volume (IDV) and ICK via 15 Gy IDV minus the 20 Gy IDV. Contributions of each IDV to the PTV coverage were analyzed along with normal brain toxicity due to the patient setup uncertainty. Induced uncertainty and minimum dose covering the entire PTV were analyzed to determine the maximum tolerable patient setup errors to utilize the ICK effect for radiosurgery of m-bm via SIMT-VMAT. RESULTS: Patient setup errors of 1.3 mm /1.3° in all six directions must be maintained to achieve PTV coverage of the 15 Gy IDV for ICK. Setup errors of ±2 mm/2° showed clinically unacceptable loss of PTV coverage of 29.4 ± 14.6% even accounting the ICK effect. However, no clinically significant effect on normal brain dosimetry was observed. CONCLUSIONS: Radiosurgery of m-bm using SIMT-VMAT treatments have shown positive clinical outcomes even with small residual patient setup errors. These clinical outcomes, while largely due to DCK, may also potentially be due to the ICK. Potential mechanisms, such as devascularization and/or radiation-induced intratumor immune enhancement, should be explored to provide a better understanding of the radiobiological response of stereotactic radiosurgery of m-bm using a SIMT-VMAT plan

Evaluation of Plan Quality and Treatment Efficiency for Single-Isocenter/Two-Lesion Lung Stereotactic Body Radiation Therapy

Purpose/objectives: To evaluate the plan quality and treatment delivery efficiency of single‐isocenter/two‐lesions volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT). Materials/methods: Eight consecutive patients with two peripherally located early stage nonsmall‐cell‐lung cancer (NSCLC) lung lesions underwent single‐isocenter highly conformal noncoplanar VMAT SBRT treatment in our institution. A single‐isocenter was placed between the two lesions. Doses were 54 or 50 Gy in 3 and 5 fractions respectively. Patients were treated every other day. Plans were calculated in Eclipse with AcurosXB algorithm and normalized to at least 95% of the planning target volume (PTV) receiving 100% of the prescribed dose. For comparison, two‐isocenter plans (isocenter placed centrally in each target) were retrospectively created. Conformity indices (CIs), heterogeneity index (HI), gradient index (GI), gradient distance (GD), and D2cm were calculated. The normal lung V5, V10, V20, mean lung dose (MLD) and other organs at risk (OARs) doses were evaluated. Total number of monitor units (MUs), beam‐on time, and patient‐specific quality assurance (QA) results were recorded. Results: The mean isocenter to tumor distance was 6.7 ± 2.3 cm. The mean combined PTV was 44.0 ± 23.4 cc. There was no clinically significant difference in CI, HI, GD, GI, D2cm, and V20 including most of the OARs between single‐isocenter and two‐isocenter lung SBRT plans, evaluated per RTOG guidelines. However, for single‐isocenter plans as the distance between the lesions increased, the V5, V10, and MLD increased, marginally. The total number of MUs and beam‐on time was reduced by a factor of 1.5 for a single‐isocenter plan compared to a two‐isocenter plan. The single‐isocenter/two‐lesions VMAT lung SBRT QA plans demonstrated an accurate dose delivery of 98.1 ± 3.2% for clinical gamma passing rate of 3%/3 mm. Conclusion: The SBRT treatment of two peripherally located lung lesions with a centrally placed single‐isocenter was dosimetrically equivalent to two‐isocenter plans. Faster treatment delivery for single‐isocenter treatment can improve patient compliance and reduce the amount of intrafraction motion errors for well‐suited patients

Feasibility of Using Ring-Mounted Halcyon Linac for Single-Isocenter/Two-Lesion Lung Stereotactic Body Radiation Therapy

PURPOSE: To demonstrate the plan quality and delivery efficiency of volumetric-modulated arc therapy (VMAT) with the Halcyon Linac ring delivery system (RDS) in the treatment of single-isocenter/two-lesion lung stereotactic body radiation therapy (SBRT). MATERIALS/METHODS: Sixteen previously treated non-coplanar VMAT single-isocenter/two-lesion lung SBRT plans delivered with SBRT-dedicated C-arm TrueBeam Linac were selected. Prescribed dose was 50 Gy to each lesion over five fractions with treatment delivery every other day and AcurosXB algorithm as the final dose calculation algorithm. TrueBeam single-isocenter plans were reoptimized for Halcyon Linac with coplanar geometry. Both TrueBeam and Halcyon plans were normalized for identical combined target coverage and evaluated. Conformity indices (CIs), heterogeneity index (HI), gradient index (GI), gradient distance (GD), and D2cm were compared. The normal lung V5Gy, V10Gy, V20Gy, mean lung dose (MLD), and dose to organs at risk (OAR) were evaluated. Treatment delivery parameters, including beam-on time, were recorded. RESULTS: Halcyon plans were statistically similar to clinically delivered TrueBeam plans. No statistical differences in target conformity, dose heterogeneity, or intermediate-dose spillage were observed (all, p \u3e 0.05). Halcyon plans, on average, demonstrated statistically insignificant reduced maximum dose to most adjacent OAR and normal lung. However, Halcyon yielded statistically significant lower maximal dose to the ribs (p = 0.041) and heart (p = 0.026), dose to 1 cc of ribs (p = 0.035) and dose to 5 cc of esophagus (p = 0.043). Plan complexity slightly increased as seen in the average increase of total monitor units, modulation factor, and beam-on time by 480, 0.48, and 2.78 min, respectively. However, the estimated overall treatment time was reduced by 2.22 min, on average. Mean dose delivery accuracy of clinical TrueBeam plans and the corresponding Halcyon plans was 98.9 ± 0.85% (range: 98.1%–100%) and 98.45 ± 0.99% (range: 97.9%–100%), respectively, demonstrating similar treatment delivery accuracy. CONCLUSION: SBRT treatment of synchronous lung lesions via single-isocenter VMAT on Halcyon RDS is feasible and dosimetrically equivalent to clinically delivered TrueBeam plans. Halcyon provides excellent plan quality and shorter overall treatment time that may improve patient compliance, reduce intrafraction movement, improve clinic efficiency, and potentially offering lung SBRT treatments for underserved patients on a Halcyon only clinic

Fast Generation of Lung SBRT Plans with a Knowledge-Based Planning Model on Ring-Mounted Halcyon Linac

PURPOSE: To demonstrate fast treatment planning feasibility of stereotactic body radiation therapy (SBRT) for centrally located lung tumors on Halcyon Linac via a previously validated knowledge-based planning (KBP) model to support offline adaptive radiotherapy. MATERIALS/METHODS: Twenty previously treated non-coplanar volumetric-modulated arc therapy (VMAT) lung SBRT plans (c-Truebeam) on SBRT-dedicated C-arm Truebeam Linac were selected. Patients received 50 Gy in five fractions. c-Truebeam plans were re-optimized for Halcyon manually (m-Halcyon) and with KBP model (k-Halcyon). Both m-Halcyon and k-Halcyon plans were normalized for identical or better target coverage than clinical c-Truebeam plans and compared for target conformity, dose heterogeneity, dose fall-off, and dose tolerances to the organs-at-risk (OAR). Treatment delivery parameters and planning times were evaluated. RESULTS: k-Halcyon plans were dosimetrically similar or better than m-Halcyon and c-Truebeam plans. k-Halcyon and m-Halcyon plan comparisons are presented with respect to c-Truebeam. Differences in conformity index were statistically insignificant in k-Halcyon and on average 0.02 higher (p = 0.04) in m-Halcyon plans. Gradient index was on average 0.43 (p = 0.006) lower and 0.27 (p = 0.02) higher for k-Halcyon and m-Halcyon, respectively. Maximal dose 2 cm away in any direction from target was statistically insignificant. k-Halcyon increased maximal target dose on average by 2.9 Gy (p \u3c 0.001). Mean lung dose was on average reduced by 0.10 Gy (p = 0.004) in k-Halcyon and increased by 0.14 Gy (p \u3c 0.001) in m-Halcyon plans. k-Halcyon plans lowered bronchial tree dose on average by 1.2 Gy. Beam-on-time (BOT) was increased by 2.85 and 1.67 min, on average for k-Halcyon and m-Halcyon, respectively. k-Halcyon plans were generated in under 30 min compared to estimated dedicated 180 ± 30 min for m-Halcyon or c-Truebeam plan. CONCLUSION: k-Halcyon plans were generated in under 30 min with excellent plan quality. This adaptable KBP model supports high-volume clinics in the expansion or transfer of lung SBRT patients to Halcyon

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic