Volumetric Modulated Arc Therapy Plans Research Articles

Updating approach for lexicographic optimization-based planning to improve cervical cancer plan quality

BackgroundTo investigate the capability of a not-yet commercially available fully automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), to further improve the plan quality of an already-validated Wish List (WL) pushing on the organs-at-risk (OAR) sparing without compromising target coverage and plan delivery accuracy.Material and MethodsTwenty-four mono-institutional consecutive cervical cancer Volumetric-Modulated Arc Therapy (VMAT) plans delivered between November 2019 and April 2022 (50 Gy/25 fractions) have been retrospectively selected. In mCycle the LO planning algorithm was combined with the a-priori multi-criterial optimization (MCO). Two versions of WL have been defined to reproduce manual plans (WL01), and to improve the OAR sparing without affecting minimum target coverage and plan delivery accuracy (WL02). Robust WLs have been tuned using a subset of 4 randomly selected patients. The remaining plans have been automatically re-planned by using the designed WLs. Manual plans (MP) and mCycle plans (mCP01 and mCP02) were compared in terms of dose distributions, complexity, delivery accuracy, and clinical acceptability. Two senior physicians independently performed a blind clinical evaluation, ranking the three competing plans. Furthermore, a previous defined global quality index has been used to gather into a single score the plan quality evaluation.ResultsThe WL tweaking requests 5 and 3 working days for the WL01 and the WL02, respectively. The re-planning took in both cases 3 working days. mCP01 best performed in terms of target coverage (PTV V95% (%): MP 98.0 [95.6–99.3], mCP01 99.2 [89.7–99.9], mCP02 96.9 [89.4–99.5]), while mCP02 showed a large OAR sparing improvement, especially in the rectum parameters (e.g., Rectum D50% (Gy): MP 41.7 [30.2–47.0], mCP01 40.3 [31.4–45.8], mCP02 32.6 [26.9–42.6]). An increase in plan complexity has been registered in mCPs without affecting plan delivery accuracy. In the blind comparisons, all automated plans were considered clinically acceptable, and mCPs were preferred over MP in 90% of cases. Globally, automated plans registered a plan quality score at least comparable to MP.ConclusionsThis study showed the flexibility of the Lexicographic approach in creating more demanding Wish Lists able to potentially minimize toxicities in RT plans.

Prospective Dosimetric Comparison Study Between Volumetric Modulated Arc Therapy and Intracavitary Brachytherapy for Cervical Cancer

Although volumetric modulated arc therapy (VMAT) boost can achieve highly conformal dose distributions for cervical cancer, VMAT has the disadvantage of requiring set-up and organ motion margins. This study prospectively recruited patients with the cervical cancer and compared VMAT plan with intracavitary brachytherapy (ICBT) plan. All patients treated with ICBT for locally advanced cervical cancer between April 2020 and September 2022 were enrolled. Patients had whole-pelvis radiotherapy, followed by CT scans with and without the tandem and ovoid in the same session (for the planning of ICBT and VMAT, respectively). ICBT planning characterizes the high-risk clinical target volume (HR-CTV) as the target volume and the bladder, rectum, sigmoid colon and small bowel loop as the organ at risk (OAR). VMAT planning defines the HR-CTV + 3 mm as the target volume and bladder, rectum + 3 mm (planning organ at risk volume (PRV) rectum), sigmoid colon + 3 mm (PRV sigmoid) and bowel bag as the OAR to account for set-up and organ motion. ICBT and VMAT plans were optimized for maximal dose received by at least 90% (D90%) of the target volume without impairing the dose constraints for the OARs. The prescribed dose (PD) was 26 Gy in 4 fractions. The dose constraints were determined as 25.2 Gy for D2 ml in the bladder and 20 Gy for D2 ml in the other OARs. The D90% and D100% of the target volume and D2 ml of OARs were compared between 2 plans using paired two-tailed Student's t test. Seventeen patients were enrolled. Dose and volume parameters for the 2 plans are shown in Table 1. Of the 17 patients, D90% of the target volume received 100% PD in 4 cases with ICBT plans, in 6 cases for VMAT plans, and in 2 cases with both methods. For D90% of the target volume, ICBT plans were greater than VMAT plans in 4 cases, with a maximum difference of 5.6 Gy (ICBT: 26.0 Gy, SBRT: 20.4 Gy). VMAT plans were higher than ICBT plans in 11 cases, with a maximum difference of 10.3 Gy (ICBT: 14.5 Gy, SBRT: 24.8 Gy). The dose-limiting OARs to attain D90% of target volume were bladder in 12 cases and small bowel loop in 1 case for ICBT plans, while PRV rectum in 11 cases, PRV sigmoid in 4 cases and bowel bag in 1 case for VMAT plans. This prospective study with 17 ICBT-eligible patients revealed D90% of the target volume demonstrated no substantial difference between VMAT and ICBT plans, while D100% showed a significant increase in VMAT plan compared to ICBT plan. Even with a set-up and organ motion margins on the HR-CTV and OARs, VMAT may have a dosimetric advantage over ICBT if the target geometry is complicated and close to the OARs.

Dosimetric Validation of 3D-Printed Bolus at Different Printing Infill Percentage in VMAT Plan

The 3D printed bolus technology is rapidly evolving in external beam radiotherapy and printing parameters can have a significant impact on absorbed dose. In this study, a novel 3D printed bolus was designed to evaluate the time and material cost effects, dosimetry differences, and surface dose modulation capabilities in the volumetric-modulated arc therapy (VMAT) plan at different print filling percentages. A hollow-type bolus, the middle 2.36 mm of 5 mm thickness infilled with different ratio, was designed and printed with polylactic acid (PLA). The ratio of printed material was defined by the infill percentage parameter ranging from 10% to 90%. For each bolus, two treatment plans were designed with AAA algorithm, considering the real computed tomography (CT) scan of the 3D printed bolus and modeling the 3D printed bolus as a virtual bolus structure. Percentage depth dose (PDD) profiles were calculated to build up the mapping equivalent CT value in treatment plan system (TPS). Measurement dose was performed by radiographic films. The PDD profiles were then compared between measured and calculated. A simulation VMAT treatment plan with planning target volume (PTV) close to the body surface was designed on a water-equivalent phantom, and the modulation capabilities of epidermal dose under different filling percentage was compared. Compared with 100% percent infill 3D printed bolus, The maximum printing time could be reduced by 47.8% and material consumption could be reduced by 42.5%. The surface dose at single field irradiation can reach 69.6% to 85.8% of the maximum dose in different filling boluses. The PDD measurement and mapping equivalent CT calculation deviation was less than 3% when the infill percentage of the middle region is greater than 30%. The dose distribution of the VMAT plan is satisfying for infill percentages greater than 30%. Using the 3D printing technology is possible to modulate the amount of shift of the build-up region by tuning the infill percentage of the 3D printed bolus. Patients could undergo CT simulation without bolus. Appropriate bolus could be selected according to the location of the PTV region and dose requirement.

Comparative Dosimetry for Hippocampal-Avoidant Whole Brain Radiotherapy with Helical Tomotherapy and VMAT Planning Techniques

The advent of hippocampal-avoidant whole brain radiotherapy (HA-WBRT) has allowed for substantial improvements in cognition without compromising the efficacy of palliative whole brain radiotherapy. Volumetric modulated arc therapy (VMAT), a form of rotational intensity-modulated radiation therapy (IMRT), allows for rapid treatment delivery and minimizes fractional treatment time. However, given the intrinsic complexity of HA-WBRT planning, standard VMAT techniques require significant departmental resources and often fail to achieve planning objectives. We hypothesize that treatment planning and delivery on a helical tomotherapy (HT) unit improves OAR dosimetry compared to standard VMAT techniques. Patients with multiple brain metastases who received WBRT with palliative intent were included in this single institution dosimetric study. Treatment objectives and dose constraints for HA-WBRT from NRG CC001 were utilized. Three separate plans were generated for each patient including Dual-Arc Conventional VMAT (DAC), Split-Arc Partial-Field VMAT (SAPF), and HT for dosimetric comparison. VMAT plans were generated using 6-MV photon beams with a maximum dose rate of 600 MU/min with a 120-leaf MLC. DAC plans utilized 2 coplanar arcs each with jaw tracking. SAPF plans used four partial arcs, and the field size of each beam was reduced to allow the MLC to block the centrally located hippocampus without sacrificing the whole brain PTV coverage. HT plans with a dose rate of 1000MU/min and Helical Delivery mode used a 2.5cm dynamic Jaw setting. Mean differences in target volume coverage and OAR dosimetry between planning approaches were calculated. Two-tailed, paired Student's t-tests were employed to determine statistically significant differences between DAC, SAPF, and HT plans. A total of 15 treatment plans were generated for five patients (5 DAC, 5 SAPF, and 5 HT plans). HT was seen to significantly reduce hippocampal D100% compared to both DAC (∆-114.16 cGy, p = 0.001) and SAPF (∆-125.76 cGy, p < 0.001). Moreover, HT hippocampal D0.03cc was significantly lower than DAC (∆-80.26 cGy p = 0.003) and SAPF (∆-174.40 cGy, p < 0.001). At the same time, PTV coverage as determined by D98% was significantly higher compared to both DAC (∆ +372.66 cGy, p = <0.001) and SAPF (∆ +304 cGy, p = <0.001). Compared to both DAC and SAPF, HT planning for HA-WBRT provides significant improvements in target coverage and OAR sparing. Additional research is warranted to determine whether further reductions in dose to the hippocampi provide additional clinical benefit.

Proton Based Stereotactic Radiotherapy for Skull Base Patients: Dosimetric Comparison to 4 Modern Radiation Treatment Modalities

Re-irradiation with ablative doses to a smaller target volume and strict critical structure constraint is a challenge for modern radiation planning and delivery systems. Several advanced radiation treatment techniques can be used for fractionated stereotactic ablative radiosurgery (FSRS) in select patients with unresectable recurrent head and neck tumors. In this study, in order to better understand the dosimetry advantage of each technique, we compare the stereotactic treatment plans of our new small spot size Hitachi proton treatment unit to those of CyberKnife stereotactic radiosurgery (CK), Gamma Knife radiosurgery (GK), volumetric modulated arc therapy (VMAT), and MR Linac radiotherapy (MRL). Ten FSRS skull base patients treated at our institution using VMAT (n = 5) or GK (n = 5) techniques. Intensity-modulated proton therapy (IMPT) plans were created in Raystation using Monte Carlo dose calculation algorithm. VMAT, CK, GK and MRL plans were generated in RayStation, Accuray Precision, Leksell Gamma Plan, and Monaco treatment planning systems, separately. Planning goals were to achieve the best target coverage of prescribed dose without compromising the critical organs at risk dose volume constraints of the clinical treatment plans. Plans were compared based on percent CTV coverage, Paddick conformity index (PCI), gradient index (GI, V50/V100), dose homogeneity index (HI, (D2-D98)/D50), low dose bath volume (LDBV, ratio of total volume irradiated between 20% and 50% prescription dose and the target volume), beam-on-time (BOT), and mean/maximum doses to brainstems. The median target volume was 15.5 cm3 (range 1.0 - 36.23 cm3). The prescription was 45 Gy in 5 fractions for VMAT patients, and 21 - 27 Gy in 3 fractions for GK patients. The comparison of the treatment plans of these 5 delivery modalities was shown in table. All techniques achieved comparable CTV coverage. GI was superior for GK plans and outstanding in CK and IMPT plans. IMPT plans were also outstanding in regard to BOT and PCI. Significantly improved HI, LDBV and brainstem mean doses were achieved in IMPT plans. For adjacent brainstem and other OARs, maximum doses were comparable among all techniques. In these five advanced radiation therapy modalities, proton therapy SBRT showed dosimetric advantage over other modalities to spare nearby OARs without sacrifice of target coverage. Further studies are needed to utilize this clinical benefit and investigate plan robustness.

Feasibility and Safety of Single-Isocenter/Multi-Lesion (SIML) HyperArc Brain SRT: Clinical Implementation and Early Outcomes

Patients with multiple brain metastases may not tolerate relatively longer treatment times for traditional stereotactic radiation therapy (SRT) with individual isocenter plans for each lesion due to discomfort or co-morbidities. SRT using a single-isocenter/multi-lesion (SIML) HyperArc volumetric modulated arc therapy (VMAT) plan with flattening filter free (FFF) beam could significantly shorten overall treatment time, and improve patient comfort, compliance, and clinic efficiency. We report early clinical results of treating multiple brain metastases with SIML HyperArc SRT. Twenty-three patients with multiple brain metastatic tumors (range, 2-9 lesions; total treated lesions, n = 96) were simulated using Encompass support and Q-fix mask, and treated with a highly-conformal SIML VMAT SRT plans via non-coplanar HyperArc geometry. Mean tumor distance to isocenter was 5.3 cm, maximum up to 7 cm. Common prescriptions were 25-30 Gy/5 fractions, 24-27 Gy/3 fractions, and 20 Gy/1 fraction prescribed to each planning target volume (PTV) using 2 mm margin around standard gross tumor volume (GTV) delineated on contrasted enhanced MP-RAGE MRI fusion. Acuros dose calculation for 6MV-FFF beam was used for tissue heterogeneity corrections. Alliance A071801 criteria was used for dose constraints to organs at risk (OAR) and target conformality. Treatment was delivered every other day with CBCT-guidance, adjustments made with 6DOF couch corrections on a medical linear accelerator, and treatment delivery time within 15 minutes. Local control rates were reported, and toxicity profile rated based on CTCAE v5.0 for brain radionecrosis, optic neuropathy, and brainstem dysfunction. All plans met Alliance A071801 requirements for each tumor coverage, dose to OAR including optic apparatus, brainstem, and spinal cord. Mean GTV and PTV volume were 9.4 cc (range, 0.3-54.8 cc) and 16.13 cc (range, 1.0-80.2 cc). Patient-specific quality assurance results were 98.3% for gamma passing criteria of 2%/2mm. Independent in-house Monte Carlo physics second check agreed with HyperArc plans by ±3.0%. Mean follow up was 6 months (range, 0.0-18.6 months). Of the 23 patients treated, 17 (74%) had post-treatment MRI imaging to assess local control and toxicity. Local control was achieved in 69/73 (95%) of treated and followed lesions. CTCAE grade 2 radionecrosis occurred in 2 patients and were managed with dexamethasone. No CTCAE grade 3+ events of radionecrosis, optic pathway dysfunction, or brainstem toxicity were observed. SIML HyperArc Brain SRT for multiple brain metastases has excellent local control and low toxicity profile in our patients. It can significantly reduce treatment delivery time as compared to traditional multiple-isocenter brain SRT or chronologically separate treatment courses and thus, help to improve patient comfort, compliance, ease of care, and clinic workflow. Longer median follow up of SIML brain SRT on larger patient cohort is warranted.

Advancing beyond the Hippocampus to Preserve Cognition for Patients with Brain Metastases: Dosimetric Results from a Phase 2 Trial of Memory-Avoidance Whole Brain Radiotherapy

Recent advances to preserve neurocognitive function in patients treated for brain metastases include stereotactic radiosurgery (SRS), hippocampal avoidance whole brain radiation therapy (HA-WBRT), and memantine administration. However, 23% of patients receiving HA-WBRT and memantine on NRG-CC001 still experienced executive function deterioration at 4 months, with 12% experiencing total recall and delayed recognition deterioration at 6 months. The hippocampus, corpus callosum, fornix, and amygdala are key neurocognitive substructures with a low propensity for brain metastases. Herein, we report our preliminary experience using an advanced "memory-avoidance" WBRT (MA-WBRT) approach sparing these substructures for patients with multiple (>15) brain metastases. Ten consecutive patients treated with MA-WBRT on a phase 2 clinical trial (OSU-21074) were reviewed. In each patient, the hippocampi, amygdalae, corpus callosa, and fornix were contoured. Patients were not eligible for MA-WBRT if they had metastases in these substructures. A memory- avoidance region created using a 5mm volumetric expansion around these substructures. Hotspots were avoided in the hypothalamus and pituitary gland. Dose constraints for these avoidance structures were modeled after NRG CC-001 and include a D100% ≤ 9 Gy and a D0.03 cc ≤ 16 (acceptable to 20 Gy). Coverage of brain metastases was prioritized over memory avoidance dose constraints. Linac-based volumetric modulated arc therapy (VMAT) plans were generated for a prescription dose of 30 Gy in 10 fractions. On average, the memory avoidance structure volume was 37.1 ccs (Range: 25.2-44.6 ccs), occupying 2.5% of the entire whole brain target volume. All treatment plans met the D100% dose constraint, and 8/10 plans met the D0.03cc constraint, with priority given to tumor coverage for the remaining 2 cases. VMAT spared the memory avoidance structures with a median dose range of 10.8-14.2 Gy and a maximum dose (D0.03cc) range of 15.6-22.7 Gy. The mean dose to the memory avoidance structures was 12.7 Gy (Range: 11.5-13.8 Gy). Target coverage (D98% > 25 Gy) and homogeneity (D2% ≤ 37.5 Gy) were achieved for all plans. Modern VMAT techniques allow for sparing of the hippocampus, amygdala, corpus callosum, and fornix with good target coverage and homogeneity. Prospective quality of life and cognitive data including are being collected and include the Functional Assessment of Cancer Therapy - Brain (Fact-Br), Hopkins Verbal Learning Test (HLVT-R), Trail Making Test A/B (TMT-A/B) and Controlled Oral Word Association Test (COWAT). After enrollment is completed, these data will be evaluated to assess the efficacy of MA-WBRT to mitigate declines in quality of life and cognition after whole brain radiation.

Plan Comparison of Left Breast Postmastectomy Radiotherapy: Halcyon IMRT and VMAT Plan vs. Truebeam Fixed-Jaws Plan

The purpose of this work is to provide a Varian Halcyon planning solution for left breast postmastectomy radiotherapy by comparing the plan quality of Varian Truebeam plan with Halcyon plan. Ten patients who previously received left breast postmastectomy intensity-modulated radiotherapy (IMRT) on Truebeam were retrospectively selected and replanned using Halcyon. The planning target volume (PTV) included chest wall and supraclavicular region, and the prescribed dose was 50 Gy in 25 fractions (2 Gy/F). In addition to the original Truebeam fixed-jaws IMRT (IMRT_T), a Halcyon IMRT (IMRT_H) plan and a Halcyon volumetric-modulated arc therapy (VMAT_H) plan were designed for each patient. The conformity index (CI) and homogeneity index (HI) of the PTVs, and the dose of organs at risk were calculated and compared. Statistical significance was performed using the LSD-t test or Wilcoxon signed-rank test with a significance level of 0.05. The V20 and V30 of ipsilateral lung, the V20, V30 and Dmean of heart, and CI of target area in IMRT_H plan were significantly lower than those in IMRT_T plan (P<0.05). No significant difference was found in the V5, V10 and Dmean of ipsilateral lung, the V5 and Dmean of contralateral lung, the V5 and Dmean of contralateral breast, HI of PTV (P>0.05), but the Dmean of left humeral head in IMRT_H plan was significantly higher than that of IMRT_T plan (P<0.05). All the metrics mentioned above showed higher level in VMAT_H plan than the IMRT_T plan and IMRT_H plan (P<0.05), except for HI (P>0.05) and Dmean of left humeral head (P>0.05 when compared to IMRT_H plan). The IMRT_H plan acts better in OAR sparing and PTV conformity than the IMRT_T plan, while the VMAT-H plan can only parallel the other two techniques in HI. The IMRT_H plan is promising in treating left breast postmastectomy patients with dosimetric improvements.

Comparison of Dynamic Trajectory Radiotherapy and Volumetric Modulated Arc Therapy for Loco-Regionally Advanced Oropharyngeal Cancer

Dynamic trajectory radiotherapy (DTRT) extends volumetric modulated arc therapy (VMAT) with dynamic table and collimator rotation. We investigate the potential benefit of DTRT over VMAT with respect to organ-at-risk (OAR) sparing for patients with loco-regionally advanced oropharyngeal cancer (OPC). We created DTRT and VMAT plans for 46 cases with prescribed doses of 50-70 Gy (2 Gy fractions, sequential boost) using 6 MV flattened beam on c-arm Linacs. For DTRT: case-specific collision avoidance maps were created and gantry-table paths were determined based on contoured structures to minimize fractional target/OAR overlap in beam's eye view. Gantry-collimator paths minimized field width in the leaf-travel direction. DTRT paths were imported in a research version of a commercial treatment planning system for intensity modulation optimization using the same optimizer and dose calculation algorithms as for VMAT. Plans at each dose level were normalized with 100% of the prescribed dose to 95% of the planning target volume (PTV). PTV coverage and OAR sparing for DTRT and VMAT were compared using Wilcoxon matched-pair signed rank test (5% significance level). The correlation between the fractional OAR/PTV50Gy volume overlap and difference in OAR Dmean between the two techniques was evaluated using Spearman's correlation coefficient. Plans at each dose level were all acceptable and had D0.03cc<110% prescription dose (difference between DTRT and VMAT were not statistically significant). In the combined plans, PTV50Gy D95% and D98% and PTV70Gy D95% were significantly higher with DTRT compared to VMAT. Differences in PTV66Gy coverage and PTV70Gy D5% were not statistically significant. Mean Dmean to the contralateral (CL) parotid gland was 13.99 / 15.28 Gy for DTRT / VMAT respectively, it was 25.75 / 28.05 Gy for the CL submandibular gland, 44.88 / 45.82 Gy for the pharynx and 30.90 / 33.93 Gy for the oral cavity (all with p<.001). Mean Dmean to the ipsilateral (IL) parotid gland was 29.00 / 29.28 Gy for DTRT / VMAT respectively (p = .77) and 57.71 / 57.91 Gy for the IL submandibular gland (p = .99). Significantly higher doses were observed with DTRT than with VMAT for the optical and auditory OARs and for the brain, but well below the clinical goals. The difference in Dmean (VMAT-DTRT) was negatively correlated to the fractional OAR/PTV50Gy overlap for the CL parotid and submandibular gland and the IL submandibular gland (r = -0.55 to -0.51, p<.001) but not for IL parotid gland (r = -0.17, p = .26), oral cavity (r = -0.13, p = .41) or pharynx (r = -011, p = .47). For at least the same target coverage, DTRT statistically significantly improves sparing for OARs related to salivary and swallowing functions compared to state-of-the-art VMAT. The advantage of DTRT decreases with increasing fractional OAR/PTV50Gy volume overlap for some salivary glands but not for pharynx or oral cavity. DTRT is promising to reduce treatment-related toxicity for patients with OPC.

Feasibility Study of Robust Treatment Planning in VMAT for Head and Neck Cancer

In general, patient positional uncertainty is considered by adding a geometrically expanded margin to clinical target volume (CTV) in photon radiation therapy. However, this method may not be suitable because image-guided radiotherapy is available. In intensity modulated proton beam therapy, robust treatment planning is currently common to take patient positional uncertainty into account in optimization rather than in margins. The purpose of this study is to assess the feasibility of clinical implementation of the method in volumetric modulated arc therapy (VMAT) for head and neck cancer. We quantitatively evaluated whether the plans with the robust optimization (Robust plans) can adequately cover CTV against patients' positional uncertainties and body shape change throughout a treatment course. Ten head and neck cancer patients were chosen, who were treated with PTV-based VMAT plans in our hospital between 2021.5-2022.4. RayStation V10A (RaySearch Laboratories, Stockholm, Sweden) was used for the robust optimization, which was applied to the CTVs with patient positional uncertainty of 5 mm in the 6-axis direction. Dose prescribed to the high- and low-risk CTVs were to 70 and 56 Gy in 35 fractions, respectively. To create the patients' CT images with residual set-up errors and body shape change at the treatment, pseudo simulation-CT images were created by deformable image registration with CBCT and simulation-CT. Dose distribution at the treatment was re-calculated by applying the plan to the pseudo simulation-CT images. The variation of D98 for the high-risk CTV from the time of treatment planning was evaluated on a weekly basis. For comparison, planning target volume (PTV) -based plans (5 mm margin circumference) were created and a similar evaluation was performed. D98 for the high-risk CTV varied between -3∼2% in the robust plan and between -5∼1% in the PTV-based plan during the treatment course. There was no significant difference in the amount of D98 variation between the two plans by t-test, except for one case with hypopharyngeal cancer. In this case, D98 for the high-risk CTV varied within ±1% with the PTV-based plan, whereas the value decreased up to 3% with the robust plan (p < 0.05). This case often had a residual setup error of approximately 5 mm at the sites related to the pitch rotation of head, suggesting that the dose distribution for the robust plan was affected by non-rigid positional errors. Patient weight loss during the treatment period was -3.5±2.4 kg, showing a weak correlation (r = -0.33) with the variation in D98 for the high-risk CTV. The robust treatment planning exhibits comparable CTV coverage to the conventional PTV-based planning against positional uncertainty and body shape change throughout a treatment period. In order to overcome set-up baseline shift by the non-rigid positional errors, re-planning should be recommended. Further planning studies will be conducted to promote clinical implementation of the method.

New Advantage in Stereotactic Treatment of Lung and Pancreatic Cancer. Performance of Ultra-High Energy Electron (VHEE) Therapy Adjuvanted to the FLASH Effect: Clinical Implications and Treatment Plans Analysis

Very High-Energy Electron (VHEE) beams delivered at ultra-high dose rates and hence profiting from the FLASH effect, may be a viable alternative to conventional treatment plans for the treatment of deep-seated tumors. Experimental data support the evidence of a considerable normal tissue sparing effect when treatments are delivered with dose rates much larger (100 times or more) compared to the conventional ones. Lung cancer and pancreatic cancer are considered the two biggest cancer killers. We urgently need more research in these areas, more awareness that support improvement in treatment strategies. To evaluate the potential of FLASH VHEE irradiation in these two clinical situations, we investigated the achievable sparing of healthy tissues and critical dose-limiting structures, with the goal of performing a higher dose prescription. The study on the potential of VHEE for the stereotactic treatment of pancreatic and lung lesions was carried out on two clinical cases treated with Volumetric Modulated Arc Therapy (VMAT) techniques at University Hospital Campus Bio-Medico of Rome. The Planning Target Volume (PTV) was identified and the constraints on the Organs at Risk (OAR) and details on the irradiation approach were defined. The VHEE plan was designed to optimize the dose delivery to best activate the modelled FLASH effect based on the current experimental knowledge. In particular the impact on a dose threshold to activate the effect was studied. The VHEE treatment plan was based on an accurate Monte Carlo simulation of the electrons interactions and the results achievable with different FLASH effect models were studied. The simulation allowed the estimation of dose maps, which were used as input to an optimization algorithm that modified the fluence of each beam to meet treatment prescriptions in terms of dose to PTV. At the end the VHEE DVH plans were compared to VMAT plans. The results demonstrated that FLASH therapy with VHEE beams of 70-130 MeV, could represent a promising alternative to standard radiotherapy allowing a comparable sparing of the healthy tissues. In the case of pancreatic cancer, the Dose Volume Histograms (DVH) showed how such a technique can be effective in sparing the duodenum. In case of lung cancers, the result showed how pulmonary tissue sparing can lead to a substantial reduction of pulmonary toxicity in comparison with the VMAT technique. In the case of pancreatic cancer and assuming a non-negligible contribution from the FLASH effect, the DVH showed how the duodenum healthy tissue sparing could allow a higher dose to be prescribed at the target while keeping the constraints respected, improving the therapeutic ratio. In the case of lung cancer, the advantages of the technique are additionally increased by the significant benefit that could be related to the treatment delivery time reduction (<1s) and to the corresponding advantage coming from a reduced organ movement that translates in a lower risk of lung toxicity.

Changes in Target Coverage and Dose to the Normal Brain during Fractionated Stereotactic Radiotherapy for Metastatic Brain Tumors

Fractionated stereotactic radiotherapy (SRT) has been applied to large brain metastases to reduce the risk of radiation necrosis. For fractionated SRT, potential of interfractional tumor changes during the treatment period, such as tumor size, shape, and geometry, must be considered to improve the tumor local control. Our center performs adaptive re-planning for large brain metastases based on repeat MRI verification with a contrast agent in the middle of the treatment period. Purpose of this study is to evaluate the dosimetric impact of the changes in tumor size, shape, and geometry on the doses to the targets and normal brain in patients with brain metastases undergoing fractionated SRT. Fifteen solitary large intracranial metastatic lesions treated with fractionated SRT were investigated. Standardized planning MRI (MRI-1) and repeat verification MRI (MRI-2) were performed during the middle of the irradiation period. The GTV on the MRI-1 and MRI-2 scans was contoured by the same oncologist. The PTV was created by adding an isotropic margin of 1 mm from the GTV in all directions. Volumetric modulated arc therapy (VMAT) with beam energies of 6 MV (flattening filter-free mode) was used and plans were normalized such that PTV D95% or D98% was equal to the prescribed dose. Beam configuration and intensity on the initial VMAT plan were used to evaluate the dose to the tumor and the normal brain on MRI-2. We evaluated the impact of D98% on the GTV using the plans on the MRI-1 and MRI-2 scans. For the normal brain, the V90%, V80%, and V50% were investigated. The median GTV changed from 9.8 cc (range of 3.2-33.0 cc) to 9.7 cc (range of 2.8-36.5 cc) (p = 0.482). Three and four tumors exhibited volume shrinkage and enlargement changes of >10%. Five tumors exhibited volume shrinkage and enlargement changes of <10%. Three tumors showed no volume changes. Of the 15 large brain metastases, 12 tumors required treatment plan modification. The dosimetric parameters of the GTV, PTV, and normal brain did not significantly differ between the MRI-1 and MRI-2 scans. Regarding the tumor dose, the D98% to the GTV increased in patients with tumor shrinkage because of dose inhomogeneity and decreased in patients with tumor enlargement. The V90%, V80%, and V50% increase with decreasing tumor volumes and were linearly related to the tumor volume difference, with a coefficient of determination of 0.97, 0.98, and 0.97, respectively. Our study demonstrated the usefulness of repeat verification MRI for adaptive radiotherapy in the middle of the treatment period due to changes in tumor size, shape, and geometry in patients with brain metastases. Repeated MRI should be considered to evaluate the dose to the target and normal brain, which improves tumor local control and reduces brain necrosis, to reduce the magnitude of underdosing to the target or overdosing to the normal brain during the treatment period.

Dosimetric evaluation of accelerated partial breast irradiation (APBI) using volumetric modulated arc therapy (VMAT) technique

Purpose: Five-fraction radiation therapy treatment regimens for accelerated partial breast irradiation (APBI) using intensity modulated radiotherapy (IMRT) have become increasingly used after several phase three trials demonstrated similar or reduced toxicity compared with whole breast irradiation. Improving the treatment efficiency of this technique could significantly improve delivery accuracy and tolerability, especially for treatment plans utilizing deep inspiration breath hold (DIBH) technique. The aim of this study was to determine the optimal technique for APBI, with a focus on volumetric modulated arc therapy technique (VMAT) and flattening-filter free (FFF) delivery. Methods: Ten APBI cases, five cases each left and right breast, were randomly selected. Each case was contoured following guidelines included in the APBI-IMRT-Florence Trial and planned to use both non-coplanar static-field IMRT with standard flattened-filter (FF) beam and VMAT techniques with both FF and FFF beam. For each VMAT plan, two partial arcs were used with patient-specific start and stop angles. Arc extents emulated opposed tangential fields and were chosen based on target and organ at risk (OAR) locations. Evaluated OARs included the heart, ipsilateral and contralateral lung, and normal breast. All plans were generated using the Eclipse treatment planning system (Version 15.6). A prescription dose of 30Gy delivered in 5 fractions was used for all cases. Plans were compared and evaluated using several dose metrics as well as treatment time. Results: For targets, VMAT exhibited similar coverage (V95%) but higher Dmax compared to IMRT (105% (IMRT) v.s .111% (VMAT), p=0.002. VMAT provided similar OAR avoidance compared to IMRT for the heart (Dmean, V3Gy, V0.5Gy), ipsilateral lung (V10Gy), contralateral lung (V5Gy) and contralateral breast Dmax within 10cGy/2% (p~0.005). VMAT contributed slightly lower dose outside the target in the ipsilateral breast, with an average difference in V15Gy of approximately 8% (37% (IMRT) v.s. 29% (VMAT)). Finally, because IMRT delivery is non-coplanar, and typically requires at least 5 treatment fields, co-planar VMAT reduced the total treatment significantly. VMAT with FF beam energies also used fewer monitor unites compared to IMRT with FF beam energies. The utilization of FFF beam energies for VMAT further improved delivery time compared to IMRT. Overall, VMAT with FFF beam energies reduced treatment time by approximately 20% compared to IMRT with FF beam. Conclusions: Co-planar partial-arc FFF VMAT technique produced equivalent target coverage, improved efficiency, better normal tissue sparing, and shorter delivery time compared to non-coplanar IMRT technique. Shorter delivery time also assists in the reduction of patient motion associated with breath hold. VMAT technique with FFF delivery is a suitable replacement for IMRT in APBI.

Deep learning-based dose prediction to improve the plan quality of volumetric modulated arc therapy for gynecologic cancers.

In recent years, deep-learning models have been used to predict entire three-dimensional dose distributions. However, the usability of dose predictions to improve plan quality should be further investigated. To develop a deep-learning model to predict high-quality dose distributions for volumetric modulated arc therapy (VMAT) plans for patients with gynecologic cancer and to evaluate their usability in driving plan quality improvements. A total of 79 VMAT plans for the female pelvis were used to train (47 plans), validate (16 plans), and test (16 plans) 3D dense dilated U-Net models to predict 3D dose distributions. The models received the normalized CT scan, dose prescription, and target and normal tissue contours as inputs. Three models were used to predict the dose distributions for plans in the test set. A radiation oncologist specializing in the treatment of gynecologic cancers scored the test set predictions using a 5-point scale (5, acceptable as-is; 4, prefer minor edits; 3, minor edits needed; 2, major edits needed; and 1, unacceptable). The clinical plans for which the dose predictions indicated that improvements could be made were reoptimized with constraints extracted from the predictions. The predicted dose distributions in the test set were of comparable quality to the clinical plans. The mean voxel-wise dose difference was -0.14±0.46Gy. The percentage dose differences in the predicted target metrics of and were -1.05%±0.59% and 0.21%±0.28%, respectively. The dose differences in the predicted organ at risk mean and maximum doses were -0.30±1.66Gy and -0.42±2.07Gy, respectively. A radiation oncologist deemed all of the predicted dose distributions clinically acceptable; 12 received a score of 5, and four received a score of 4. Replanning of flagged plans (five plans) showed that the original plans could be further optimized to give dose distributions close to the predicted dose distributions. Deep-learning dose prediction can be used to predict high-quality and clinically acceptable dose distributions for VMAT female pelvis plans, which can then be used to identify plans that can be improved with additional optimization.

Effect of simultaneous integrated boost concepts on photoneutron and distant out-of-field doses in VMAT for prostate cancer.

Asimultaneous integrated boost (SIB) may result in increased out-of-field (DOOF) and photoneutron (HPN) doses in volumetric modulated arc therapy (VMAT) for prostate cancer (PCA). This work therefore aimed to compare DOOF and HPN in flattened (FLAT) and flattening filter-free (FFF) 6‑MV and 10-MV VMAT treatment plans with and without SIB. Eight groups of 30VMAT plans for PCA with 6MV or 10MV, with or without FF and with uniform (2 Gy) or SIB target dose (2.5/3.0 Gy) prescriptions (CONV, SIB), were generated. All 240 plans were delivered on aslab-phantom and compared with respect to measured DOOF and HPN in 61.8 cm distance from the isocenter. The 6‑and 10-MV flattened VMAT plans with conventional fractionation (6-and 10-MV FLAT CONV) served as standard reference groups. Doses were analyzed as afunction of delivered monitor units (MU) and weighted equivalent square field size Aeq. Pearson's correlation coefficients between the presented quantities were determined. The SIB plans resulted in decreased HPN over an entire prostate RT treatment course (10-MV SIB vs. CONV -38.2%). Omission of the flattening filter yielded less HPN (10-MV CONV -17.2%; 10-MV SIB -22.5%). The SIB decreased DOOF likewise by 39% for all given scenarios, while the FFF mode reduced DOOF on average by 60%. Astrong Pearson correlation was found between MU and HPN (r > 0.9) as well as DOOF (0.7 < r < 0.9). For acomplete treatment, SIB reduces both photoneutron and OOF doses to almost the same extent as FFF deliveries. It is recommended to apply moderately hypofractionated 6‑MV SIB FFF-VMAT when considering photoneutron or OOF doses.

Robust mixed electron-photon radiation therapy planning for soft tissue sarcoma.

Mixed electron-photon beam radiation therapy (MBRT) is an emerging technique in which external electron and photon beams are simultaneously optimized into a single treatment plan. MBRT exploits the steep dose falloff and high surface dose of electrons while maintaining target conformity by leveraging the sharp penumbra ofphotons. This study investigates the dosimetric benefits of MBRT for soft tissue sarcoma (STS)patients. A retrospective cohort of 22 STS of the lower extremity treated with conventional photon-based Volumetric Modulated Arc Therapy (VMAT) were replanned with MBRT. Both VMAT and MBRT treatments were planned on the Varian TrueBeam linac using the Millenium multi-leaf collimator. No electron applicator, cutout or additional collimating devices were used for electron beams of MBRT plans. MBRT plans were optimized to use a combination of 6 MV photons and five electron energies (6, 9, 12, 16, 20 MeV) by a robust column generation algorithm. Electron beams in this study were planned at standard 100 cm source-axis distance (SAD). The dose to the clinical target volume (CTV), bone, normal tissue strip and other organs-at-risk (OARs) were compared using a Wilcoxon signed-ranktest. As part of the original VMAT treatment, tissue-equivalent bolus was required in 10 of the 22 patients. MBRT plans did not require bolus by virtue of the higher electron entrance dose. CTV coverage by the prescription dose was found to be clinically equivalent between plans of either modality: (MBRT) = 97.9 ± 0.2% versus (VMAT) = 98.1 ± 0.6% (p=0.34). Evaluating the absolute paired difference between doses to OARs in MBRT and VMAT plans, we observed lower to normal tissue in MBRT plans by 14.9 ± 3.2% ( ). Similarly, to bone was found to be decreased by 8.2 ± 4.0% ( ) of the bonevolume. For STS with subcutaneous involvement, MBRT offers statistically significant sparing of OARs without sacrificing target coverage when compared to VMAT. MBRT plans are deliverable on conventional linacs without the use of electron applicators, shortened source-to-surface distance (SSD) or bolus. This study shows that MBRT is a logistically feasible technique with clear dosimetricbenefits.

Dosimetric Evaluation Study of 10-MV FFF Used in SBRT for Lung Tumours

Purpose: The objective of this research was to conduct a comparative and dosimetric analysis of three different radiotherapy techniques used in lung stereotactic body radiotherapy (SBRT), the three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT), using a 10 MV flattening filter-free (FFF) photon beam. Materials and methods: The present study employed computed tomography (CT) images of a humanoid phantom for the purpose of treatment planning. The gross tumour volumes (GTVs) delineated in both the central and peripheral positions of the lungs. The determination of Planning Target Volumes (PTVs) involved the addition of a margin of 0.5 cm to the Gross Tumour Volume (GTV). Three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) treatment plans produced employing a 10-megavolt (MV) flattening filter-free (FFF) photon beam. The calculation of dosage for all plans Performed using the anisotropic analytical algorithm (AAA). Results: IMRT and VMAT had better PTV dose conformation than 3DCRT for both central and peripheral targets. PTV conformity improved in VMAT compared to IMRT, and CI values were acceptable for VMAT, IMRT, and 3DCRT plans. VMAT plans had slightly better CI than IMRT, with better results in peripheral lung PTVs compared to central PTVs. VMAT and IMRT are superior for treating HDV and D2cm, with lower HDV for peripheral lung tumours. Both 3DCRT and IMRT improved outcomes for peripheral lung PTVs, while VMAT was better for central lung PTVs. The former proved better with less low lung doses and improved D2cm results. 3DCRT plans demonstrated higher precision in dose distribution than VMAT and IMRT plans, with superior average GI values. VMAT and IMRT had higher HI, Dmax, and D2% than 3DCRT. VMAT plans compared to IMRT plans, with similar HI values for central lung PTVs. VMAT better spares OARs than other techniques, but V20 and V30 lung doses were lower with 3DCRT. VMAT increases lung dose, but OAR stays below thresholds.&#x0D; Conclusion: The investigation found that all three treatment techniques can deliver SBRT plans that meet RTOG dose constraints. However, VMAT is a better treatment strategy than IMRT and 3DCRT for both peripheral and central lung PTVs, based on dosimetric indices like CI, D2cm, HI, and HDV. The study found that 3DCRT improves dosimetric indices, especially gradient index (GI), more than VMAT. Despite the need for more monitor units (MUs) in VMAT plans, treatment time reduced due to faster gantry velocity and higher dose rates (2400cGy/min) via free flatting filter energy.

Study on the transferability of the knowledge-based VMAT model to predict IMRT plans in prostate cancer radiotherapy

ObjectiveThe aim of this study was to investigate the feasibility of VMAT library-derived model transfer in the prediction of IMRT plans by dosimetry comparison among with three groups of IMRT plans: two groups of automatic IMRT plans generated by the knowledge-based the volumetric modulated arc therapy (VMAT) model and intensity-modulated radiation therapy (IMRT) model and one group of manual IMRT plans.Methods52 prostate cancer patients who had completed radiotherapy were selected and randomly divided into 2 groups with 40 and 12 separately. Then both VMAT and IMRT plans were manually designed for all patients. The total plans in the group with 40 cases as training datasets were added to the knowledge-based planning (KBP) models for learning and finally obtained VMAT and IMRT training models. Another 12 cases were selected as the validation group to be used to generated auto IMRT plans by KBP VMAT and IMRT models. At last, the radiotherapy plans from three groups were obtained: the automated IMRT plan (V-IMRT) predicted by the VMAT model, the automated IMRT plan (I-IMRT) predicted by the IMRT model and the manual IMRT plan (M-IMRT) designed before. The dosimetric parameters of planning target volume (PTV) and organ at risks (OARs) as well as the time parameters (monitor unit, MU) were statistically analyzed.ResultsThe dose limit of all plans in the training datasets met the clinical requirements. Compared with the training plans added to VMAT model, the dosimetry parameters have no statistical differences in PTV (P > 0.05); the dose of X% volume (Dx%) with D25% and D35% in rectal and the maximum dose (Dmax) in the right femoral head were lower (P = 0.04, P = 0.01, P = 0.00) while D50% in rectal was higher (< 0.05) in the IMRT model plans. In the 12 validation cases, both automated plans showed better dose distribution compared with the M-IMRT plan: the Dmax of PTV in the I-IMRT plans and the dose in volume of interesting (VOI) of bladder and bilateral femoral heads were lower with a statistically significant difference (P < 0.05). Compared with the I-IMRT plans, dosimetric parameters in PTV and VOI of all OARs had no statistically significant differences (P > 0.05), but the Dmax in left femoral heard and D15% in the right femoral head were lower and have significant differences (P < 0.05). Furthermore, the low-dose regions, which was defined as all volumes outside of the PTV (RV) with the statistical parameters of mean dose (Dmean), the volume of covering more than 5 Gy dose (V5Gy), and also the time parameter (MU) required to perform the plan were considered. The results showed that Dmean in V-IMRT was smaller than that in the I-IMRT plan (P = 0.02) and there was no significant difference in V5Gy and MU (P > 0.05).ConclusionCompared with the manual plan, the IMRT plans generated by the KBP models had a significant advantage in dose control of both OARs and PTV. Compared to the I-IMRT plans, the V-IMRT plans was not only without significant disadvantages, but it also achieved slightly better control of the low-dose region, which meet the clinical requirements and can used in the clinical treatment. This study demonstrates that it is feasible to transfer the KBP VMAT model in the prediction of IMRT plans.

Impact of magnetic resonance imaging-related geometric distortion of dose distribution in fractionated stereotactic radiotherapy in patients with brain metastases.

The geometric distortion related to magnetic resonance (MR) imaging in adiagnostic radiology (MRDR) and radiotherapy (MRRT) setup is evaluated, and the dosimetric impact of MR distortion on fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases is simulated. An anthropomorphic skull phantom was scanned using a1.5‑T MR scanner, and the magnitude of MR distortion was calculated with (MRDR-DC and MRRT-DC) and without (MRDR-nDC and MRRT-nDC) distortion-correction algorithms. Automated noncoplanar volumetric modulated arc therapy (HyperArc, HA; Varian Medical Systems, Palo Alto, CA, USA) plans were generated for 53patients with 186 brain metastases. The MR distortion at each gross tumor volume (GTV) was calculated using the distance between the center of the GTV and the MR image isocenter (MIC) and the quadratic regression curve derived from the phantom study (MRRT-DC and MRRT-nDC). Subsequently, the radiation isocenter of the HA plans was shifted according to the MR distortion at each GTV (HADC and HAnDC). The median MR distortions were approximately 0.1 mm when the distance from the MIC was < 30 mm, whereas the median distortion varied widely when the distance was > 60 mm (0.23, 0.47, 0.37, and 0.57 mm in MRDR-DC, MRDR-nDC, MRRT-DC, and MRRT-nDC, respectively). The dose to the 98% of the GTV volume (D98%) decreased as the distance from the MIC increased. In the HADC plans, the relative dose difference of D98% was less than 5% when the GTV was located within 70 mm from the MIC, whereas the underdose of GTV exceeded 5% when it was 48 mm (-26.5% at maximum) away from the MIC in the HAnDC plans. Use of adistortion-correction algorithm in the studied MR diagnoses is essential, and the dosimetric impact of MR distortion is not negligible, particularly for tumors located far away from the MIC.

Establishment and interpretation of the gamma pass rate prediction model based on radiomics for different intensity-modulated radiotherapy techniques in the pelvis

Backgroundand objectives: Implementation of patient-specific quality assurance (PSQA) is a crucial aspect of precise radiotherapy. Various machine learning-based models have showed potential as virtual quality assurance tools, being capable of accurately predicting the dose verification results of fixed-beam intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) plans, thereby ensuring safe and efficient treatment for patients. However, there has been no research yet that simultaneously integrates different IMRT techniques to predict the gamma pass rate (GPR) and explain the model.Methods: Retrospective analysis of the 3D dosimetric verification results based on measurements with gamma pass rate criteria of 3%/2 mm and 10% dose threshold of 409 pelvic IMRT and VMAT plans was carried out. Radiomics features were extracted from the dose files, from which the XGBoost algorithm based on SHapley Additive exPlanations (SHAP) values was used to select the optimal feature subset as the input for the prediction model. The study employed four different machine learning algorithms, namely, random forest (RF), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM), to construct predictive models. Sensitivity, specificity, F1 score, and AUC value were calculated to evaluate the classification performance of these models. The SHAP values were utilized to perform a related interpretive analysis on the best performing model.Results: The sensitivities and specificities of the RF, AdaBoost, XGBoost, and LightGBM models were 0.96, 0.82, 0.93, and 0.89, and 0.38, 0.54, 0.62, and 0.62, respectively. The F1 scores and area under the curve (AUC) values were 0.86, 0.81, 0.88, and 0.86, and 0.81, 0.77, 0.85, and 0.83, respectively. The explanation of the model output based on SHAP values can provide a reference basis for medical physicists when adjusting the plan, thereby improving the efficiency and quality of treatment plans.Conclusion: It is feasible to use a machine learning method based on radiomics to establish a gamma pass rate classification prediction model for IMRT and VMAT plans in the pelvis. The XGBoost model performs better in classification than the other three tree-based ensemble models, and global explanations and single-sample explanations of the model output through SHAP values may offer reference for medical physicists to provide high-quality plans, promoting the clinical application and implementation of GPR prediction models, and providing safe and efficient personalized QA management for patients.