Dose Planning Research Articles

Online Adaptive Radiotherapy for Pharyngeal Cancer: Dose-Volume Histogram Analysis between Adapted and Scheduled Plan

The present study aimed to evaluate whether online adapted plan with artificial intelligence (AI) driven work flow could be used in clinical settings with variable changes of the targets and organs at risk (OARs) for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy at our institution between January and July 2020 were included for the analysis. All patients had been previously aligned daily with cone-beam computed tomography (CBCT) and treated by O-ring Linac. A simulated treatment was performed on the treatment emulator. Weekly fractions, once in every 4-5 fractions, were simulated in the treatment emulator for each patient using their previous on-treatment CBCTs. The dataset was divided into three groups according to the treatment period (1st-2nd week, 20 CBCTs), middle (3rd-4th week, 20 CBCTs), and late (5th-7th week, 30 CBCTs) period. In the present study, all of reference plan generation in treatment emulator were created on the initial plans of two-step method using 12 equidistant field IMRT. The prescribed dose was 70 Gy in 35 fractions and normalized to the dose of 68.6 Gy (98% dose) to 95% of the planning target volume (PTV). The adaptation process on treatment emulator includes auto-segmentation of daily anatomy, calculation of the dose in scheduled plans using the same monitor units and optimization and calculation of the dose in adapted plan. Dose-volume histogram (DVH) parameters between adapted and scheduled plans in terms of PTV (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brain stem (Dmax), ipsilateral and contralateral parotid glands (Dmedian and Dmean) were evaluated in each period. D98% of PTV of adapted plan was significantly higher than that of scheduled plan in early and middle period (p = 0.02 and <0.01, respectively). D95% of PTV of adapted plan was significantly higher than that of scheduled plan in all periods (p<0.01). D2% of PTV of adapted plan was significantly lower than that of scheduled plan in all periods (p = 0.04, 0.04 and 0.02 in each period, respectively). There was not significant difference in D50% of PTV between adapted and scheduled plan in all periods. In terms of OARs, Dmax of spinal cord of adapted plan was significantly lower than that of scheduled plan in all periods (p<0.01). Similarly, D1cc of spinal cord of adapted plan was lower than that of scheduled plan. Dmean of ipsilateral and contralateral parotid glands of adapted plan were lower than those of scheduled plan in the late period (p<0.01 and 0.03, respectively). The present study revealed that adapted plan with AI driven work flow could create dosimetrically better plans for pharyngeal cancer compared to scheduled plan. It was suggested that online adaptive radiotherapy could be necessary to maintain PTV coverage while reducing the dose to OARs in all periods for pharyngeal cancer.

Knowledge Based Planning for Lung SBRT: Model Transferability between Treatment Systems and Calculation Algorithms

Knowledge based planning (KBP) is known to be effective and clinically feasible in achieving high quality treatment plans with less variability between planners and reduced planning time. A KBP model is highly dependent on characteristics of the training data. Our institution developed and validated a lung SBRT KBP model from plans treated with a C-arm linear accelerator (Linac). This study aims to evaluate the quality of lung SBRT plans with a KBP model when this model is used for an O-ring Linac with different MLC design, beam quality, and calculation algorithm. Two academic hospitals in the same healthcare network were included in this study. One hospital trained a KBP model for five-fraction lung SBRT using 43 plans calculated using the Eclipse AcurosXB v15.6 algorithm for a C-arm Linac. The model was developed to prioritize dose gradient outside the PTV while satisfying institutional critical organ limits and validated using an additional set of 12 plans. A cohort of 10 patients (11 plans) previously treated with lung SBRT using the O-ring Linac at the second hospital was selected. These plans were calculated using the Eclipse AAA v15.6 algorithm with prescription doses of 30-50 Gy in five fractions. Each plan was re-optimized using the KBP model, without manual adjustment of the optimization objectives, using the same beam geometry as in the clinical plans. KBP plans were normalized to achieve the same PTV coverage as the clinical plans. Clinical and KBP plans were evaluated for ITV D98%, PTV conformity index (CI), R50 and maximum dose at 2 cm from the PTV (D2cm). All clinical and KBP plans met critical organ dose constraints. The range of CI was 1-1.13 vs. 0.96-1.05 for clinical plans and KBP plans, respectively. R50 and D2cm were lower with KBP plans (p = 0.007 and p = 0.05, respectively). ITV D98% range was 105-120% vs. 117-122% of the PTV prescription dose for clinical plans and KBP plans, respectively, and higher with KBP plans (p<0.001). For plans where the PTV overlaps the chest wall (n = 7), the maximum chest wall doses (D0.03cc) from KBP plans were higher than the clinical plans (p = 0.16), with an absolute chest wall D0.03cc difference of 9 Gy (54 Gy vs 63 Gy). The KBP model includes an ITV SIB of 120% of the PTV prescription, whereas the clinical plans reduced the ITV SIB when the PTV overlapped the chest wall, highlighting a difference in clinical practice between the two hospitals in this study. This study supports that a lung SBRT KBP model trained using plans for one Linac system and the AcurosXB algorithm can be used to generate clinically acceptable plans without manual planner intervention for a different Linac system and the AAA calculation algorithm, indicating the potential of a KBP model use for centralized planning process across different Linac systems and calculation algorithms.

Use of Lattice Therapy for Dose-Escalation in Palliative Treatment of Bulky Head and Neck Tumors

Palliative radiation is used to relieve pain and bleeding in patients with locally advanced head and neck cancers. Lower doses are utilized to meet normal tissue tolerances, limiting the duration of palliation. Lattice therapy can achieve intratumoral dose escalation while sparing surrounding tissues, but a standard approach does not exist. In this study, we explore the impact of variation in the values and distributions of peak and valley doses in palliative lattice treatment plans. Five-fraction volumetric-arc based (VMAT) lattice plans were generated using a customized Python v3.6 script. For each combination of peak/valley doses and sphere size and spacing, a bounding box was generated around the gross tumor volume (GTV) and divided into equal segments in the x, y, and z planes. Individual spheres were constructed for a given parameter set and those fully encompassed within the target contracted by 2 cm were used to create peak dose targets with values of 30, 40, and 50 Gy. A valley dose of 20 Gy was chosen to match standard dosing for 5-fraction palliative plans and the associated target volumes were generated by subtracting an 8 mm expansion of the peak dose spheres from the overall target volume. Multi-criteria optimization (MCO) was used to generate a final plan. The planning target volume (PTV) was a uniform 3-mm expansion from the GTV. Target volume and OAR dosimetric parameters were analyzed using Mann-Whitney U and Kruskal-Wallis testing. A total of 72 unique plans were evaluated for 4 patients with large GTV sizes ranging from 159 to 413 cm3. The median time to generate an individual plan using the automated script was 20 minutes (IQR, 18 - 23). Median values of mean GTV and PTV doses were 27.9 Gy (IQR, 24.7 - 30.3) and 26.7 Gy (IQR, 23.9 - 29.1), respectively. Further analysis was then limited to plans containing ablative 50 Gy dose spheres. For these 24 plans, mean GTV and PTV doses increased to a median of 31.7 Gy (IQR, 29.6 - 33.3) and 29.6 Gy (IQR, 27.8 - 31.0), respectively. Mean doses to 1, 2, and 4 cm expansions around the GTV for this cohort had median values of 19.5 Gy, 15.1 Gy, and 9.7 Gy, respectively. Median doses to 0.03 cc of mandible, spinal cord, and esophagus were 28.2 Gy (range, 7.0 - 35.7), 14.7 Gy (range, 9.8 - 18.8), and 8.7 Gy (range, 0.8 - 16.2), respectively. Mean GTV dose was dependent on sphere spacing (median 29.9 Gy for 4 cm spacing vs. 33.5 Gy for 3 cm, p<0.001), but not on sphere size (median 31.3 Gy for 2 cm vs. 31.8 Gy for 1.5 cm vs. 31.5 Gy for 1 cm, p = 0.968). VMAT-based lattice planning allows dose escalation to bulky head and neck tumors, including significant coverage with ablative doses while meeting normal tissue constraints. Thus, lattice plans could enhance palliation while reducing toxicity. Mean target coverage is dependent on sphere spacing. Use of automated plan generation could also facilitate clinical application.

Hippocampal Avoidance Whole BRAIN Radiotherapy (HA-WBRT) with Simultaneous Integrated BOOST (SIB) vs. HA-WBRT in Multiple Brain Metastases: A Dosimetric Comparison

There has been a paradigm shift in managing multiple brain metastases. Various options include SRS, WBRT, and WBRT with Hippocampal avoidance (HA-WBRT). There is no consensus for the treatment of multiple brain metastases (>3 brain metastases). A new technique that has proven feasible is dose escalation in the form of simultaneous integrated boost. The aim of this study was to compare the dosimetry parameters of HA-WBRT plus simultaneous integrated boost versus HA-WBRT alone in multiple brain metastases. In a prospective trial,16 patients with multiple brain metastasis (≥ 3) from various primaries with good performance scores (ECOG PS ≤ 2) are recruited. All patients underwent CT simulation (1.5 mm slice thickness) and RT plans for HA-WBRT with (SIB) and HA-WBRT alone were made. A 5 mm margin was given to the bilateral hippocampus for Hippocampal Avoidance. In the HA-WBRT plan for the PTV i.e., whole brain plus 3 mm margin minus hippocampal avoidance region (H.A.), a dose of 30 Gy in 10 fractions is prescribed over two weeks. In HA-WBRT with SIB, a dose of 30 Gy in 10 fractions over two weeks is prescribed for the PTV, which is the clinical target volume, minus the hippocampal avoidance region (H.A.) minus the PTV Mets (1 mm margin to the GTV). A simultaneous Integrated Boost of 42.5 Gy in 10 # over two weeks is prescribed for PTVmets. Planning was done using a VMAT technique with 6MV F.F.F. beam energy in a treatment planning software. The mean B/L hippocampus volume is 3.47 cc. The mean dose of PTV D98% in HA-WBRT plans is 27.45 Gy, whereas in HA-WBRT with S.I.B. is 27.36 Gy (p = 0.90). V30 mean dose in HA-WBRT plans is 93.35%, and the mean dose in HA-WBRT SIB is 91.87% (p = 0.12). PTV D2% mean dose in HA-WBRT Is 36.06 Gy, and in HA-WBRT -S.I.B., it is 40.58 (p< 0.001). The mean bilateral hippocampus Dmax in HA-WBRT is 14.85 Gy, and in HA-WBRT-SIB is 14.25 Gy (p = 0.35). The mean Bilateral hippocampus D100% is 9.14 Gy in HA-WBRT and 9.01 Gy in HA-WBRT-SIB (p = 0.54). The mean brainstem Dmax in HA-WBRT is 36.82 Gy compared to 38.55 Gy in HA-WBRT-SIB (p = 0.02). In patients planned for a simultaneous boost along with hippocampal sparing whole brain radiotherapy, the mean dose to the hippocampal region did not increase. The Dmax of Brainstem, optic chiasma is significantly higher in HA-WBRT-). Our study, the mean dose to PTVmets is more than 45 Gy and more than 50 Gy to GTV with a BED of more than 65 Gy (α/ß = 10) to the metastases, which is equivalent to some ablative dose regimens. Simultaneous integrated boost along with hippocampal sparing radiotherapy thus helps in sparing the hippocampus and delivering higher doses to the metastases and intermediate doses to the rest of the brain, addressing the microscopic disease.

Planning Considerations for the Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Radiotherapy for Locally-Advanced Non-Small Cell Lung Cancer

Phase III prospective randomized trial of primary lung tumor stereotactic body radiation therapy followed by concurrent mediastinal chemoradiation for locally-advanced non-small cell lung cancer (NRG LU-008), designed to lower the rates of radiation pneumonitis and improve the progression-free survival, is expected to become active nationally in July 2023. Due to the specific nature of the cases selected for this trial, a new approach to treatment planning had to be developed to satisfy the conditions of the trial. Levice Cancer Institute (Atrium Health, North Carolina) ran the initial Phase II trial and investigated several approaches, providing recommendations for the future dosimetry planning approach. A total of 60 patients were selected for the initial trial and treated with a combination of SBRT treatment to the primary tumor (50-54 Gy in 3-5 fractions) and conventional IMRT treatment to 60 Gy to the involved lymph nodes for patients with stage 3 or unresectable stage II NSCLC, combined with chemotherapy. Depending on the location of the primary tumor, all cases could be subdivided into no overlap between the SBRT and IMRT targets, adjacent targets, and overlapping targets. All SBRT plans were done with a 6X-FFF beam, advanced dose calculation algorithm, and 0.1 cm grid size. IMRT targets were primarily treated with VMAT plans, though a minority of cases were planned with the DMLC technique, with a 6X beam, advanced dose calculation algorithm, and 0.25 cm grid size. Various approaches to the planning included target cropping, avoidance via adjusting optimization objectives and utilizing the base dose of the SBRT plan to optimize the dose for the IMRT nodal plan. Various geometries utilized in the plan included a variation in the number of arcs, covered arc angles, and the number of beams. A significant reduction in the side effects was achieved throughout the trial, with only three patients experiencing grade 3 or higher pneumonitis, 3 patients experiencing grade 3 or higher cardiotoxicity, and 1 patient experiencing grade 3 esophagitis. For targets with no significant overlap between the primary tumor and nodal target, standard planning techniques proved to be sufficient. For the overlapping targets, the planning approach of utilizing 2 arcs, >180-degree coverage, for the SBRT plan, and using ¼ of the base SBRT dose to plan the IMRT nodal plan provided the best target coverage while achieving sufficient OAR sparing. Planning the joint SBRT-IMRT plan in the cases of a significant target overlap requires a careful approach, but is feasible with the proposed guideline and should be achievable for any center electing to participate in the NRG LU-008 trial.

Motion Effects on Spatially Fractionated Lattice Therapy

The practice of spatially fractionated radiation therapy (SFRT), such as grid and lattice, has been shown to be effective in managing large-size tumors for palliation or more recently for medium-sized tumors with definitive intents. The main feature that differentiates SFRT from standard radiation therapy is the deliberately high degree of dose heterogeneity in the gross tumor volume (GTV). The key parameter in assessing an SFRT plan is the valley-to-peak dose ratio (VPDR), which can be defined as a simple dose ratio between the low- and high-dose region in the tumor. The belief is that the healthy tissues in the low-dose regions of the tumor would serve as centers of tissue repair, while the high dose would kill the cancerous cells and induce the bystander effects. However, the compartments of low- and high-dose regions can be washed out due to motion, for example in cases when the disease is at or near the diaphragm. This work aims at examining motion effects on VPDR and equivalent uniform dose (EUD) in SFRT plans. This work focuses on the effects of sinusoidal motion in lattice therapy, a 3D version of SFRT. A lattice VMAT plan with 6X was generated using the treatment planning system. Dose vertices were placed in a body-centered tetragonal lattice in a virtual water phantom. Each vertex was 1 cm3 and received 15 Gy to at least half of its volume. The volume ratio between the lattice and the GTV is about 3%. The distance between the two nearest vertice centers is 3 cm. A sinusoidal motion was introduced in the direction along the line connecting the two nearest neighbors and was binned into 10 phases with equal time intervals. The location of the phantom in each phase was determined by its average amplitude. The effect of the motion was assessed from the sum of all the plans in the 10 bins, each being scaled down by one-tenth of the prescribed dose. Dose coverage between the static and the sum plan is compared. Their difference in the VPDR and normal tissue damage with EUD are evaluated. The EUD was calculated based on Niemierko's formalism. The LQ model was used to estimate cell survival for normal tissues with a and b values of 0.366/Gy and 0.188 Gy2, respectively. It is common to have the VPDR at around 1/3 or lower. Our study shows that it increases from 0.26 to 0.55 for the 1.5 cm motion and the EUD for normal tissue from 5 to 7 Gy. See Table 1 for more results. A large VPDR can reduce the ability of healthy tissues in the low-dose area for repair and a lower maximum dose in the vertices may diminish the bystander effects. Motion may increase VPDR and normal tissue damage. Motion techniques such as gating or tracking can be used on disease sites subjected to respiratory motion.

Automated Lattice Treatment Planning for Bulky Tumors

Spatially-fractionated radiotherapy has potential to improve local control in bulky tumors by achieving both focally high intratumoral doses and acceptable dose fall-off to surrounding normal tissues. However, a standard of care does not exist for the optimal values and distribution of peak and valley doses in treatment plans. To evaluate these questions systematically using dosimetric analyses, the number of alternative treatment plans required exceeds the practical limits of manual planning. In this study, we report an approach for automated planning of volumetric arc-based lattice therapy resulting in over 1100 unique treatment plans. An automation script was generated using Python v3.6 and imported into departmental treatment planning software. A spreadsheet was created with varying combinations of the number of fractions, peak dose, valley dose, and peak-dose sphere size and spacing for 7 patients with bulky tumors (volume range, 159-593 cc). These values were imported into the script after which all planning was automated. For each combination, a bounding box was generated around the gross tumor target volume and divided into equal segments in the x, y, and z planes. Individual spheres were constructed for a given parameter set and those fully encompassed within the target contracted by 2 cm were used to create peak dose targets. The valley dose targets were generated by subtracting an 8 mm expansion of the peak dose spheres from the overall target volume. Multi-criteria optimization (MCO) was then applied to generate a final plan after which the script moved onto the next permutation in the spreadsheet. Following the creation of each plan, the script populated the source spreadsheet with data including doses to the target, fall-off structures, and organs-at-risk. Plans which resulted in an MCO infeasibility error were also noted. A total of 1188 combinations of peak dose, valley dose, and peak-dose sphere size and spacing for 1- and 5-fraction plans were evaluated. Peak and valley doses ranged from 6 to 27 Gy and 0.4 to 20 Gy, respectively, for 1-fraction plans and 30 to 50 Gy and 2 to 20 Gy, respectively, for 5-fraction plans. This resulted in a range of peak/valley ratios from 1.35 to 67.5. Of these combinations, 594 plans were successfully generated and 594 were infeasible, most often due to sphere distribution or peak/valley dose ratios greater than 5. The median time for generation of an individual plan was 21 minutes (range, 15-46). Our script allowed the evaluation of 1188 unique combinations of spatial dose distribution using automated planning. This rapid, yet systematic, assessment of parameters for spatially-fractionated radiation will be used to inform pre-clinical and clinical studies and would not have been feasible with manual planning. Moreover, the median plan generation time of 21 minutes demonstrates potential for wider use of this script in standard clinical settings.

Evaluation of Plan Quality and Complexity for Automated Intracranial SBRT VMAT Treatment Plans

The purpose of this study was to evaluate the dosimetric quality and plan complexity of intracranial SBRT VMAT plans generated with an automated treatment planning system (TPS) compared to the standard conventional manually optimized VMAT plans. Ten clinical intracranial conventional SBRT VMAT plans manually generated using our standard TPS, (SE), were replanned using an automated VMAT radiosurgery TPS, Elements Cranial (EC). The plan target volume (PTV), OARs, prescription dose, fractionation, and beam arrangement remained constant between the corresponding plans from both systems. The PTV volume varied from 0.861cc to 40.022cc with prescription doses of 25Gy or 30Gy in 5 fractions. For each plan, PTV mean and max dose were recorded, as well as inverse Paddick conformity index (CI), gradient index (GI), and OAR mean and max doses. A Python script was used to calculate plan complexity metrics, including total MU, complexity metric, aperture irregularity metric, and modulation index total. Statistical significance of the comparisons was determined by performing a paired t-Test with α = 0.05. The results of plan quality and complexity metrics for each planning system are presented in Table 1. Dose conformality of the PTV showed no differences between plans generated with either planning system, with no statistical differences in the CI. The GI showed improvement for the automated plans, which appeared to be due to the system allowing higher PTV mean and max doses to achieve a sharper dose gradient from the target. There was a decrease in MU for the automated plans, which also correlated to statistically lower Complexity, Aperture Irregularity, and Modulation Index metrics. Differences in OAR mean and max doses between both systems were statistically insignificant. Clinically acceptable intracranial SBRT VMAT plans can be generated using an Automated TPS. Plan dosimetric quality with respect to PTV coverage and dose conformality, as well as OAR doses, were equivalent to manual plans. The automated plans were found to be less complex than manual plans, which may be related to the automated system allowing larger target dose inhomogeneity. While statistically significant differences were found between both systems, they may not be clinically relevant, and the differences could be related to the different planning techniques between systems.

The Impact of Intra-Fraction Bowel Motion on Luminal Gastrointestinal Organ at Risk Dosimetry When Using Stereotactic Adaptive Radiotherapy for Abdominal Malignancies

Daily online adaptive radiotherapy (ART) provides inter-fraction motion management of the luminal gastrointestinal (GI) structures when delivering abdominal SBRT. One potential drawback of ART is the time-consuming process, and intra-fraction GI changes from completion of the ART process to the end of treatment delivery have not been thoroughly evaluated. We explored intra-fraction bowel motion for patients receiving abdominal stereotactic adaptive radiotherapy (sART) MATERIALS/METHODS: Six patients with abdominal malignancies treated with CT-guided sART on a prospective feasibility trial had additional CBCT's acquired post-treatment (pTx-CBCT). All patients were prescribed to 50 Gy/5 fractions (fx), and the constraint for all GI OARs was V33≤0.5 cc. Time from initial CBCT (I-CBCT) used for adaptive planning to pTx-CBCT was collected. The luminal GI OAR (stomach (S), duodenum (D), small bowel (SB), and large bowel (LB)) were retrospectively contoured on pTx-CBCT. The OAR doses were compared between the I-CBCT and pTx-CBCT. The adaptive plan (PA) and initial plan (PI) doses were overlayed on the pTx-CBCT contours. The PA pTx-CBCT OAR doses were then compared to the PI pTx-CBCT OAR doses. A Boolean OAR structure of all GI OARs was evaluated to remove potential differences in structure definitions between providers. The T-test was used to compare differences in instances of D0.5cc ≥ 33 and 50 Gy. Patient charts were reviewed for grades (G) ≥ 3 toxicity. Thirty fractions (fx) of sART were delivered and pTx-CBCT were acquired in 26 fx. Mean time from I-CBCT to pTx-CBCT acquisition was 66 min (38-98 min). On average at 0.5 cc the PA overdosed the S by 1.74 Gy based on pTx-CBCT anatomy compared to 2.35 Gy by the PI, the D by 0.47 Gy (PA) vs .84 Gy (PI), the SB by 1.14 Gy (PA) vs 1.43 Gy (PI), and the LB by 0.13 Gy (PA) vs 0.60 Gy (PI). The dose to the Boolean OAR structure was on average 2.51 Gy/fx higher than expected when overlaying the PA on the pTx-CBCT compared to 3.38 Gy/fx higher when overlaying the PI on the pTx-CBCT. There was no significant difference in the instance of the PA exceeding D0.5 cc ≥33 Gy vs the PI (p = 0.083), but the PA significantly reduced the instances of D0.5cc≥50 Gy (p = 0.001) compared to the PI. No patient experienced G≥3 toxicity at a median follow-up of 8 months (3-12). These data demonstrate sART led to a significant decrease in dose to GI OARs, particularly for prescription dose or greater, even after accounting for intra-fractional bowel motion. While both the PI and the PA violated the V33 luminal GI OAR constraint in approximately ½ of pTx-CBCTs, the fraction of OARs receiving at least 50 Gy was significantly higher when overlaying the PI compared to the PA. While no G3 toxicities were reported in this small cohort, further studies are needed to characterize if the increased dose to GI OARs over the expected dose is clinically significant.

Risk-Adapted SABR for Ultra-Central Lung Tumors Attaining High BED10 to Targets in a Steep Dose-Response Window of 72-105 Gy under Tumor Tracking: A Planning Study

Higher rate of durable local control in stereotactic ablative radiotherapy (SABR) for ultra-central lung tumors (UCLTs) strongly correlates to a BED10 ≥ 100 Gy to the tumors. However, higher rates of grade 5 toxicities are reported to be directly associated with higher dose to the organs at risk (OARs) abutting or in close distance to the UCLTs, including trachea, proximal bronchial tree (PBT) and esophagus. This study evaluated two risk-adapted SABR schemes in a steep dose-response window of BED10 at 72 -105 Gy with isotoxic optimization and dynamic tumor tracking to safely attain high BED10 to the tumors while keeping dose to the OARs within evidence-based tolerances. A total of 12-16 patients are included for planning under two risk-adapted-SABR schemes of 60 Gy in 8 (scheme A) and15 (scheme B) fractions to attain high BED10 of ≥100 Gy to the distal sections of the PTV and yet potent BED10 at 72-84 Gy to the proximal sections of the PTV. Such inhomogeneous dose plans use a 3-5 mm GTV to PTV margins under a scenario that patients have at least one fiducial marker placed in or near the GTV for real-time tumor tracking on a robotic SRS-SABR system. All plans used fixed cone collimators and a planning tool's dose calculation to reach highest BED10 dose coverage achievable to the target volumes while respecting the OAR dose tolerances, including V105 Gy, V100 Gy, V84 Gy and V72 Gy in BED10 for target volumes and the maximum EQD2 dose tolerances (α/β = 3 Gy) in D0.03cc for the trachea/PBT ≤80.5-82.5 Gy and esophagus ≤64.0-77.6 Gy in scheme-A; and trachea/PBT≤97.7 Gy and esophagus ≤64.3 Gy in scheme-B. Median and range of plan dosimetry metrics are compared between the two schemes. For scheme-A, mean BED10 to PTV are 118.0 Gy (median) in105.5-133.5 Gy (range), and mean BED10 dose to GTV are 132.2 (118.3-149.4 Gy). EQD2 dose to trachea are 80.5 Gy (68.0-81.7 Gy), PBT 80.5 Gy (49.1-82.2 Gy), esophagus 67.2 Gy (51.6-77.3 Gy). PTV coverage by BED10 of 72 Gy, 84 Gy, 100 Gy and 105 Gy are 98.9% (87.5-100%), 97.1% (81.8-99.8%), 91.9% (72.5-98.6%) and 85.3% (68.5-97.9%). For scheme-B, mean BED10 to PTV are 102.2 Gy (93.4-106.0 Gy), and mean BED10 dose to GTV are 115.4 (103.4-117.3 Gy). EQD2 dose to trachea are 73.3 Gy (67.5-96.3 Gy), PBT 90.9 Gy (74.4-97.2 Gy), esophagus 61.4 Gy (41.9-64.1 Gy). PTV coverage by BED10 of 72 Gy, 84 Gy, 100 Gy and 105 Gy are 100% (94.9-100%), 95.5% (83.9-99.0%), 54.8% (31.2-65.4%) and 42.8% (17.9-53.2%). Two risk-adapted SABR of 7.5 Gyx8 and 4 Gyx15 are implemented for treating ultra-central lung tumors with BED10 ≥100 Gy to the distal sections of PTV and yet attain potent BED10 ≥72-84 Gy to the proximal sections of PTV that abut or overlap with trachea, proximal bronchial tree or esophagus. Accurate dose calculation by a planning tool and real-time tumor tracking are essential for safe and accurate delivery of such high-risk SABR treatments.

Implementation of a Patient Specific QA Protocol for a Novel Dedicated Stereotactic Radiosurgery Linear Accelerator

To describe the patient specific QA (Quality Assurance) protocol implemented for plan integrity verification, in stereotactic radiosurgery (SRS) and radiotherapy (SRT) treatments performed on a novel dedicated frameless image guided radiosurgery system using conical collimator, and a combination of yoked gimbals to cover near2pi solid angle. Startup and commissioning results obtained for planned vs measured dose distributions with several detectors are presented. The patient specific QA protocol includes: A) Review of the approved plan based on AAPM TG 275 report recommendations B) 1D verification using small volume ionization chambers inside an anthropomorphic head phantom C) 2D dose verification of a coronal and sagittal dose plan performed with high resolution 2D Array and respective phantom apparatus D) In-house independent MU (Monitor Unit) calculation using the same formalism of the vendor TPS (Treatment Planning Systems) RayTracing dose-calculation algorithm E) Monte Carlo based secondary dose check & plan QA. A retrospective analysis of the results of the first 15 patients treated is presented, focusing on plan complexity vs QA results. The 1D results obtained for the 15 SRS plans were within ±5% for all reported cases, with a mean percent difference of -1,25%, confirming an overall good agreement and, as expected, a partial volume effect in plans with smaller collimators. For the 2D dose verifications, with a 10% dose threshold, gamma passing rates of 97,5% (coronal) and 96,78 (sagittal) with 3% 1mm criteria, 95,1% (coronal) and 94,3% (sagittal) for 2% 1 mm criteria and 90,7% (coronal) and 90,0% (sagittal) for 1% 1mm criteria were obtained. Moreover, the results showed a correlation between lesion volume or number of collimators used with gamma passing rates. All MU verification results were within ±0,3% and provides an efficient risk mitigation approach for this new delivery technique. The verification results of the first 15 treated SRS plans confirmed point dose and planar measurements in agreement with TPS calculations, with superior results for planes with smaller lesions and fewer collimators. This also represents an integral validation of the image-based alignment system and fine treatment couch movements, as treatments are intrinsically multi-isocentric.

Reinforcement Learning Powered Station Parameter Optimized Radiation Therapy (SPORT): A Novel Treatment Planning and Beam Delivery Technique

Conventional intensity modulated radiation therapy (IMRT) with a typical 5-20 fixed beams often does not provide sufficient angular sampling required for conformal dose shaping, whereas current volumetric modulated arc therapy (VMAT) discretizes the angular space into equally spaced control points without considering the differential need for intensity modulation of different angles, leading to undersampling at some angles while oversampling at some other angles. Our goal is to develop a node or station parameter optimized radiation therapy (SPORT) strategy with simultaneously optimized angular sampling and beam modulation by leveraging state-of-the-art reinforcement learning and the unique capability of modern digital LINACs in dose delivery through programmable nodal points. We developed a SPORT optimization framework, in which, the process of programming control points (or station parameters) was formulated as a stochastic dynamic programming problem, which was solved by a reinforcement learning-based algorithm. On-policy reinforcement learning method, namely, state-action-reward-state-action (SARSA) was integrated with deep convolutional neural network to predict station parameters by utilizing the patient's anatomical structures meanwhile considering the delivery capability of a typical digital LINAC machine. Here, the deep convolutional neural network estimated the state-action value by using the quality of the plan with current station parameters when a next potential station parameter was selected. The state-action value was then updated by SARSA learning. The quality of the plan was quantified by dosimetry constraints. The model was assessed by a retrospective study on a cohort of patients underwent head-and-neck radiation therapy. Dosimetric analysis and delivery efficiency comparisons were used to evaluate the performance of the proposed framework. Our model was used to generate 16 plans unseen in the original training set. All the plans predicted by our model achieved better dose distributions without violating clinical planning constraints. Moreover, instead of using 4 full standard arcs in the original clinically used plans obtained via manual optimization, the predicted plans only used one full standard arc (about 178 control points) plus boost from a few sub-arcs (less than 30 degrees of gantry angles), which significantly improved the efficiency of the beam delivery. We are in the process of integrating the sub-arcs into the full arc by considering the programmable capability of modern LINACs. We demonstrated that a machine learning-based SPORT framework capable of optimizing the spatial sampling and beam modulation simultaneously for modern radiation therapy. The framework not only significantly improves the quality and efficiency of beam delivery, but also has the potential to be incorporated into current clinical workflow to improve the efficiency of dose planning and delivery.

Pelvis Treatment Plan Dose Comparison for Proton Therapy Using Single Energy and Dual Energy Computed Tomography Simulation Methods

In proton therapy, plan robustness is ameliorated by expanding the irradiation volume beyond the target, in order to mitigate setup and proton range uncertainties (RU). A byproduct of this expansion is elevated doses to surrounding organs at risk (OARs) which reduce some of the benefits associated with proton therapy. Dual-energy CT (DECT) has been shown in multiple phantom and animal tissue studies to reduce RU without compromising plan robustness. This study quantifies dosimetric differences between single-energy CT (SECT) and DECT for pelvis patients treated with intensity modulated proton therapy (IMPT). Under IRB approval, SECT and DECT scans from 25 IMPT pelvis patients were acquired using a CT scanner. Clinical plans were generated on the SECT images using robust optimization settings of 3.5% RU and 5 mm setup uncertainty in a treatment planning system. Subsequently, the clinical plans were recomputed on the corresponding DECT generated SPR-map images. For each patient, target coverage, mean and maximum OAR doses were compared for both image sets. Comparison of two plans showed systematic differences in target minimum dose (D99%) and V100%. Variations as high as 3.1% with DECT were observed in D99% indicating target under-dosage. On average, use of SECT overestimated V100% by 2.4% when compared to DECT. Since all clinical plans were optimized robustly to meet V95% coverage, higher agreement (<1%) was achieved for V95% (99.9±0.2%), and D95% (99.6±0.3%). DECT relative to SECT indicated slightly higher OAR maximum doses for femoral heads (2.3±2.78%), penile bulb/external genital (1.33±4.00%) and large bowel (0.5±1.25%). Similarly, higher mean dose was observed to rectum (2.08±4.88%), bladder (1.41±0.25%), femoral heads (1.18±6.61%) and penile bulb/external genital (1.78±5.74%) for DECT relative to SECT. Our results show a disparity between evaluated SECT and DECT target and OAR dosimetric parameters. Given the higher accuracies in proton range estimation associated with the use of DECT, its use can imply a potential for more conformal proton plans as well as higher TPS computed target coverage and OAR dose accuracy, both of which enhance overall treatment quality.

Dosimetric Study of Total Marrow and Lymphoid Irradiation on a Ring Gantry-Based Medical Linac with a Two-Layer Multi-Leaf Collimator

In this study, we aimed to evaluate dosimetric quality of total marrow and lymphoid irradiation (TMLI) plans for a ring gantry-based medical Linac with a two-layer multi-leaf collimator. We retrospectively retrieved treatment planning CT images, structure sets, and plan dose for four adult patients, two male and two female, who previously received TMLI treatments on helical tomotherapy (HT) at our institution. TMLI plans were optimized for a ring gantry-based medical Linac with a two-layer multi-leaf collimator (Halcyon, Varian Medical Systems, Inc., Palo Alto, CA). A prescription dose of 12 Gy in 8 fractions was prescribed to the skeletal bones from the skull to mid-thigh, spleen, spinal canal, and lymphoid volume. Five or six isocenters were placed with equal spacing along the patient's longitudinal direction in each TMLI plan with two 6-MV flattening filter-free volumetric modulated arc therapy (VMAT) fields at each isocenter. Isocenter separation ranged from 15 cm to 16.5 cm. Each VMAT field has a field size of 28 cm to 28 cm with the collimator at 90° and a full gantry rotation. The nominal dose rate was 800 MU/minute, and the maximum gantry rotation speed was 24°/sec. Institutional dosimetric constraints were used for optimization including a mean lung dose limit of less than 8 Gy. All the plans were normalized so that 85% the primary planning target volume received the prescription dose. The average mean doses to the target volumes ranged from 12.2 to 12.6 Gy in the Halcyon TMLI plans, while they ranged from 12.1 to 12.5 Gy in the HT TMLI plans. Relative to the prescription dose, the average mean dose for normal organs ranged from 21.3% to 56.6% in the Halcyon TMLI plans, while it ranged from 10.1% to 68.4% in the clinical HT plans. The difference in the average mean dose to normal organs was less than 0.5 Gy except two organs between the Halcyon and HT TMLI plans. The average median dose for normal organs ranged from 18.2% to 48.8% relative to the prescription dose in the Halcyon TMLI plans. The mean lung dose (MLD) in the Halcyon TMLI plans met the institutional limit with an average dose of 6.75±0.42 Gy (range: 6.44 - 7.36 Gy), while the average MLD was 6.54±0.77 Gy (range: 6.24 - 7.22 Gy) in the HT plans (p-value = 0.71 in the paired t-test). The average total monitor unit in the Halcyon TMLI plans was 4,425±906 MU (range: 3,470 - 5,575 MU) with an average beam-on time of 5.1±1.3 minutes (range: 4.1 - 7.0 minutes), which excludes isocenter setup time, while the average beam-on time was 22.2±3.2 minutes (range: 19.6 - 26.1 minutes) with the HT plans. Halcyon TMLI plans met our institutional dosimetric constraints with adequate normal organ sparing and target dose coverage. The beam-on time with the Halcyon plans was significantly shorter than that with the HT plans, which could lead to shorter treatment time and increased patient comfort. This study showed the feasibility of TMLI treatments on the Halcyon machine. The same method could be used for total body irradiation on Halcyon.

Study on Lattice Radiotherapy Treatments (LRT) for Head and Neck Bulky Tumors

Lattice radiotherapy (LRT) exploits various effects of radiation, such as the bystander effect and the abscopal effect, and consists on the administration of high dose fraction in small areas with large tumor masses, helping to solve the problem of treating bulky disease, especially if it is located in a critical anatomical area. The optimization of LRT treatment plans is challenging due to the difficulty to generate spots of high dose within the tumor with consequent high gradient. This study compares the plan dosimetry and delivery time of two delivery techniques VMAT and CyberKnife for LRT treatments of bulky head and neck lesions. Six patients with giant head and neck tumors who received LRT at our institution were included in this study. Target and OARs were contoured following international guidelines; to allow easy identification of the desired high gradient zones, an artificial geometrical lattice structure with spherical vertices was arranged inside the target volume (GTV), and the vertices of the lattice representing the high dose boost volumes (GTVboost) were delineated. The GTVboost and GTV were prescribed to receive 12 Gy and 3 Gy, respectively in a single fraction. Separate VMAT and CyberKnife LRT plans were optimized for each patient with lattice vertex of 0.5 diameter and center-to-center distances of 1.5 cm (LRT1.5) and 3 cm (LRT3). The dose heterogeneity was measured as the peak-to-valley dose ratio (PVDR), with the traditional definition being replaced by the D10/D90 ratio, where D10 and D90 represent the doses covering 10% and 90% of the GTV, respectively. For each plan generated, the treatment delivery time, the monitor units (MU), and the PVDR were assessed. Pre-treatment plan verifications were performed with ArcCheck array and Gafchromics film for VMAT and CyberKnife, respectively, using gamma analysis criteria of 3%-3mm. The mean PVDR obtained for VMAT LRT plans were 2.0 and 2.6 for LRT1.5 and LRT3, respectively, and 3.2 and 4.7, respectively for CyberKnife LRT plans. For each pre-treatment plan dose verification, the gamma passing rate (GPR) was higher than 95.0 %; CyberKnife delivery time and MU were more than 10 times higher than that of VMAT, nevertheless, VMAT had a lower PVDR. The detailed results are shown in the table below. CyberKnife LRT has a strong ability to place the peak dose within the target, generating a higher peak-to-valley dose ratio, however its use is partially invalidated by the long beam delivery times and the resulting high MU number; the use of the VMAT LRT technique allows clinically adequate dosimetry with acceptable delivery times.

Radiological evaluation of an iodised hydrogel for prostate radiotherapy applications

PurposePhysical separation of healthy tissue and target volumes in prostate radiotherapy through the insertion of hydrogel can improve patient toxicity rates. An iodised hydrogel may provide anatomical separation of prostate and rectum while being easily visualised through radio-opacity. The aim of this study was to characterise SpaceOAR Vue™ in kilovoltage (kV) images and megavoltage (MV) radiotherapy treatment planning. MethodsTwo cassettes were 3D-printed, one filled with water and the other with SpaceOAR Vue™. Transmission dose through each cassette was measured in slab phantom geometry and compared for 6MV and 10MV photon energies. The SpaceOAR Vue™ slab phantom setup was simulated using computed tomography (CT) and a treatment plan created. The plan was calculated with the hydrogel segmented and material assignment set to water, and the resultant dose compared to corresponding measurement doses. The first 5 patients treated with SpaceOAR Vue™ were assessed with the volume and Hounsfield units (HU) of the hydrogel evaluated in CT and cone beam computed tomography (CBCT) imaging. ResultsTransmission through Water and SpaceOAR Vue™ agreed to within 0.5% for both photon energies. Furthermore, the segmentation of SpaceOAR Vue™ and material assignment to water, resulted in a plan dose that agreed to measurement to within 0.5%. Clinically, the SpaceOAR Vue™ volume and HU did not vary over patient treatment course, however was found to display differently on different kV imaging modalities. ConclusionsSpaceOAR Vue™ was found to be radio-opaque on kV images, but dosimetrically behaved similarly to water in MV treatment beams, making it suitable for clinical use.

Navigating radiopharmaceutical dynamics in Ra-223 alpha emitter radiotherapy: Implications for treatment optimization and personalization

It has recently come to light that radiotherapy with Ra-223 (alpha emitter) radionuclides can be an effective therapeutic option for a variety of different cancers. A comprehensive knowledge of biodistribution, accumulation, and clearance pathways, as well as radiopharmaceutical kinetics, is required for an accurate assessment of therapy efficacy and a reduction in the severity of any adverse effects that the treatment may cause. Using the absorbed dose, measured in mGy/MBq, researchers can explore each organ in adult male and female animals and the differential accumulation, removal rates, and clearance pathways of radiopharmaceuticals. Because of their high linear energy transfer (LET) and limited range in tissue, the use of alpha emitter radionuclides in radiotherapy has attracted substantial interest recently. These properties allow for targeted therapy with minimum damage to the healthy cells in the surrounding area. This article provides a complete literature analysis on applying alpha emitter radionuclides in radiotherapy. The review focuses on zutilizing two well-known software tools, WinAct 1.0 and IDAC-Dose 2.1, for dosimetry calculations and treatment planning. The findings highlight the significance of tailored dose planning, organ-specific adverse effects, optimum treatment regimens, the potential for combination therapies, and the advancement of radiopharmaceutical development.

Organ-aware CBCT enhancement via dual path learning for prostate cancer treatment.

Cone-beam computed tomography (CBCT) plays a crucial role in the intensity modulated radiotherapy (IMRT) of prostate cancer. However, poor image contrast and fuzzy organ boundaries pose challenges to precise targeting for dose delivery and plan reoptimization for adaptivetherapy. In this work, we aim to enhance pelvic CBCT images by translating them to high-quality CT images with a particular focus on the anatomical structures important for radiotherapy. We develop a novel dual-path learning framework, covering both global and local information, for organ-aware enhancement of the prostate, bladder and rectum. The global path learns coarse inter-modality translation at the image level. The local path learns organ-aware translation at the regional level. This dual-path learning architecture can serve as a plug-and-play module adaptable to other medical image-to-image translationframeworks. We evaluated the performance of the proposed method both quantitatively and qualitatively. The training dataset consists of unpaired 40 CBCT and 40 CT scans, the validation dataset consists of 5 paired CBCT-CT scans, and the testing dataset consists of 10 paired CBCT-CT scans. The peak signal-to-noise ratio (PSNR) between enhanced CBCT and reference CT images is 27.22 ± 1.79, and the structural similarity (SSIM) between enhanced CBCT and the reference CT images is 0.71 ± 0.03. We also compared our method with state-of-the-art image-to-image translation methods, where our method achieves the best performance. Moreover, the statistical analysis confirms that the improvements achieved by our method are statistically significant. The proposed method demonstrates its superiority in enhancing pelvic CBCT images, especially at the organ level, compared to relevant methods.

Beam mask and sliding window-facilitated deep learning-based accurate and efficient dose prediction for pencil beam scanning proton therapy.

Accurate and efficient dose calculation is essential for on-line adaptive planning in proton therapy. Deep learning (DL) has shown promising dose prediction results in photon therapy. However, there is a scarcity of DL-based dose prediction methods specifically designed for proton therapy. Successful dose prediction method for proton therapy should account for more challenging dose prediction problems in pencil beam scanning proton therapy (PBSPT) due to its sensitivity to heterogeneities. To develop a DL-based PBSPT dose prediction workflow with high accuracy and balanced complexity to support on-line adaptive proton therapy clinical decision and subsequent replanning. PBSPT plans of 103 prostate cancer patients (93 for training and the other 10 for independent testing) and 83 lung cancer patients (73 for training and the other 10 for independent testing) previously treated at our institution were included in the study, each with computed tomography scans (CTs), structure sets, and plan doses calculated by the in-house developed Monte-Carlo dose engine (considered as the ground truth in the model training and testing). For the ablation study, we designed three experiments corresponding to the following three methods: (1) Experiment 1, the conventional region of interest (ROI) (composed of targets and organs-at-risk [OARs]) method. (2) Experiment 2, the beam mask (generated by raytracing of proton beams) method to improve proton dose prediction. (3) Experiment 3, the sliding window method for the model to focus on local details to further improve proton dose prediction. A fully connected 3D-Unet was adopted as the backbone. Dose volume histogram (DVH) indices, 3D Gamma passing rates with a criterion of 3%/3mm/10%, and dice coefficients for the structures enclosed by the iso-dose lines between the predicted and the ground truth doses were used as the evaluation metrics. The calculation time for each proton dose prediction was recorded to evaluate the method's efficiency. Compared to the conventional ROI method, the beam mask method improved the agreement of DVH indices for both targets and OARs and the sliding window method further improved the agreement of the DVH indices (for lung cancer, CTV D98 absolute deviation: 0.74 ± 0.18 vs. 0.57 ± 0.21 vs. 0.54 ± 0.15 Gy[RBE], ROI vs. beam mask vs. sliding window methods, respectively). For the 3D Gamma passing rates in the target, OARs, and BODY (outside target and OARs), the beam mask method improved the passing rates in these regions and the sliding window method further improved them (for prostate cancer, targets: 96.93% ± 0.53% vs. 98.88% ± 0.49% vs. 99.97% ± 0.07%, BODY: 86.88% ± 0.74% vs. 93.21% ± 0.56% vs. 95.17% ± 0.59%). A similar trend was also observed for the dice coefficients. This trend was especially remarkable for relatively low prescription isodose lines (for lung cancer, 10% isodose line dice: 0.871 ± 0.027 vs. 0.911 ± 0.023 vs. 0.927 ± 0.017). The dose predictions for all the testing cases were completed within 0.25s. An accurate and efficient deep learning-augmented proton dose prediction framework has been developed for PBSPT, which can predict accurate dose distributions not only inside but also outside ROI efficiently. The framework can potentially further reduce the initial planning and adaptive replanning workload in PBSPT.

Dose delivery reproducibility for PBS proton treatment of breast cancer patients with and without mask immobilization

BackgroundSetup reproducibility of the tissue in the proton beam path is critical in maintaining the planned clinical target volume (CTV) dose coverage and sparing the organs at risk (OAR). In this study, we retrospectively evaluated radiation therapy dose reproducibility for proton pencil beam scanning (PBS) treatment of breast cancer patients with and without mask immobilization.MethodsNinety-four patients treated between January 2019 and September 2022 with at least one verification CT scan (V-CT) in treatment position were included for this study. All patients were set up with arms up using the Orfit AIO patient positioning system, with (69 patients) or without (25 patients) mask immobilization in chin, neck, shoulder, upper arm, and chest areas. Two to three enface or near enface single field uniform dose PBS beams were optimized using a commercial treatment planning system. Prescription doses were 25 to 60 GyRBE in 5 to 45 fractions. Treatment plan doses re-calculated on V-CTs were compared to the corresponding planned doses. Cumulative doses were also calculated for patients with at least 3 V-CTs by deform and weighted sum doses from V-CTs to corresponding P-CTs. CTV D95%, ipsilateral-lung V40%, esophagus D0.01cc, and heart mean dose were evaluated and reported as percentages of prescription doses. Differences were large dose deteriorations (LDD) if: (1) CTV (V-CT/cumulative D95%) – (Planned D95%) < − 5%; or (2) Ipsilateral-lung (V-CT/cumulative V40%) – (Planned V40%) > 5%; or (3) Esophagus (V-CT/cumulative D0.01cc) – (Planned D0.01cc) > 10%; or (4) Heart (V-CT/cumulative mean) – (Planned mean) > 1.5%.ResultsOn average, V-CT/cumulative and planned CTV/OAR dose parameter differences were less than 2.2%/1.7% and 3.4%/3.7% for masked and maskless patients, respectively. The percentages of patients with at least one CTV or OAR V-CT/cumulative dose LDD were 20.3%/25.0% and 72.0%/54.0% for masked and maskless patients, respectively.ConclusionsOn average, masked/maskless setups achieved delivered and planned CTV/OAR dose parameters agreed within 2.2%/3.7% for PBS treatment of breast cancer patients in this study. Maskless patients had higher rate of CTV/OAR LDDs compared to masked patients. Dosimetric differences large enough to raise clinical concerns in either group were able to be addressed with replannings.