Maximum Planning Target Volume Research Articles

Effects of electron density force to 1.0 and fill to 1.0 on VMAT treatment plans for lung SBRT.

The aim of this study is to determine the effect of forcing and filling the electron density (ED) to 1.0 of the planning target volume (PTV) overdose distribution in lung SBRT treatment leading to shortening patient treatment time and increasing patient comfort by reducing MU/fraction due to ED manipulation effect. In this study, 36 lung SBRT plans of 12 suitable patients who prescribed a total dose of 50Gy in five fractions were generated with Monaco v.5.10 TPS using the Monte Carlo (MC) algorithm and volumetric modulated arc therapy (VMAT) technique by PTV ED values forcing as well as filling to 1.0 and comparatively assessed. The first group of plans was created by using the patient's original ED, second and third groups of plans were reoptimized by forcing and filling the ED of PTV to 1.0, respectively, therefore acquiring a new dose distribution which lead to comparatively assessment the effects of changes in ED on PTV and OAR doses. Assessment of treatment plans revealed that mean MU/fx numbers were decreased by 76% and 75.25% between Groups 1 and 2, Groups 1 and 3, respectively. The number of segments was also reduced in Group 1 by up to 15% compared with Groups 2 and 3. Maximum HI and CI differences for PTV between Groups 1 and 2 were less than 1% and Groups 1 and 3 were 1.5% which indicates all 3 group plans were comparable in terms of dose distribution within PTV. Forcing and filling the ED of PTV to 1.0 strategy has provided reduced a number of segments and MU/fx without a significant change in PTV mean and maximum doses, thereby decreasing treatment time and patient discomfort during treatment. This process should be considered in line of a potential number of patients as well as prescribed dose and MU/fx numbers.

Dosimetric evaluation of ultrafractionated dose escalation with simultaneous integrated boost to intraprostatic lesion using 1.5-Tesla MR-Linac in localized prostate cancer.

We analyzed a dose escalation of 36.25 Gy to the entire prostate and a dose increment up to 40 Gy with 1.25 Gy increments to intraprostatic lesion (IPL) using simultaneous integrated boost (SIB) in five fractions. Eighteen low- and intermediate-risk prostate cancer patients treated with 1.5T MR-Linac were retrospectively evaluated. The same planning computed tomography (CT) images generated four plans: no SIB, 37.5 Gy SIB, 38.75 Gy SIB, and 40 Gy SIB. In four plans, planning target volume (PTV) doses, organ at risk (OAR) doses, and PTV-SIB homogeneity index (HI), gradient index (GI) and conformity index (CI) were compared. All plans met the criteria for PTV and PTV-SIB coverage. PTV 40 Gy plan has higher maximum PTV and PTV-SIB doses than other plans. The PTV HI was significantly higher in the SIB 40 Gy plan (0.135 ± 0.007) compared to SIB 38.75 Gy plan (0.099 ± 0.007; p = 0.001), SIB 37.5 Gy (0.067 ± 0.008; p < 0.001), and no SIB plan (0.049 ± 0.010; p < 0.001), while there were no significant differences in HI, GI and CI for PTV-SIB between three plans. Four rectum and bladder plans had similar dosimetric parameters. The urethra D5 was significantly higher in SIB 40 Gy plan compared to no SIB plan (37.7 ± 1.1 Gy vs. 37.0 ± 0.7 Gy; p = 0.009) and SIB 37.5 Gy plan (36.9 ± 0.8 Gy; p = 0.008). There was no significant difference in monitor units between the four consecutive plans. Ultra-hypofractionated dose escalation to IPL up to 40 Gy in 5 fractions with a 1.5-T MR-linac is dosimetrically feasible, potentially paving the way for clinical trials.

Deep Learning-Based Prediction of Radiation Therapy Dose Distributions in Nasopharyngeal Carcinomas: A Preliminary Study Incorporating Multiple Features Including Images, Structures, and Dosimetry.

Purpose: Intensity-modulated radiotherapy (IMRT) is currently the most important treatment method for nasopharyngeal carcinoma (NPC). This study aimed to enhance prediction accuracy by incorporating dose information into a deep convolutional neural network (CNN) using a multichannel input method. Methods: A target conformal plan (TCP) was created based on the maximum planning target volume (PTV). Input data included TCP dose distribution, images, target structures, and organ-at-risk (OAR) information. The role of target conformal plan dose (TCPD) was assessed by comparing the TCPD-CNN (with dose information) and NonTCPD-CNN models (without dose information) using statistical analyses with the ranked Wilcoxon test (P < .05 considered significant). Results: The TCPD-CNN model showed no statistical differences in predicted target indices, except for PTV60, where differences in the D98% indicator were < 0.5%. For OARs, there were no significant differences in predicted results, except for some small-volume or closely located OARs. On comparing TCPD-CNN and NonTCPD-CNN models, TCPD-CNN's dose-volume histograms closely resembled clinical plans with higher similarity index. Mean dose differences for target structures (predicted TCPD-CNN and NonTCPD-CNN results) were within 3% of the maximum prescription dose for both models. TCPD-CNN and NonTCPD-CNN outcomes were 67.9% and 54.2%, respectively. 3D gamma pass rates of the target structures and the entire body were higher in TCPD-CNN than in the NonTCPD-CNN models (P < .05). Additional evaluation on previously unseen volumetric modulated arc therapy plans revealed that average 3D gamma pass rates of the target structures were larger than 90%. Conclusions: This study presents a novel framework for dose distribution prediction using deep learning and multichannel input, specifically incorporating TCPD information, enhancing prediction accuracy for IMRT in NPC treatment.

Intratumoral Dose Escalation Using Lattice Radiotherapy for Hepatocellular Carcinoma with Unfavorable Size and Location

Stereotactic body radiation therapy (SBRT) is a standard of care for unresectable hepatocellular carcinoma (HCC). However, its safe delivery is limited by tumor size and adjacent organs-at-risk (OARs). RTOG 1112 showed a survival benefit with local control in advanced HCC, but median dose was limited to 35 Gy in 5 fractions due to OARs. Here, we demonstrate the dosimetric feasibility of lattice radiation therapy (LRT) for dose escalation in advanced HCC. Five-fraction volumetric arc-based (VMAT) LRT 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, or 50 Gy. Valley dose target volumes over a range of 2 to 45 Gy were generated by subtracting an 8 mm expansion of the peak dose spheres from the overall target volume. Multi-criteria optimization (MCO) was applied to generate a final plan. The planning target volume (PTV) was a 5-mm uniform expansion from the GTV. All plans were generated at maximum inspiration on 4D-CT. OAR parameters were compared against a standard 5-fraction SBRT plan using Wilcoxon signed-rank testing. GTV and PTV measured 593 (23%) and 804 (32%) cm3, respectively, of a total liver volume of 2525 cm3. The minimum distance of GTV from stomach and duodenum was 6 mm and 2 mm, respectively. Plans were evaluated as per RTOG 1112 with stepwise reduction from a maximum PTV dose of 50 Gy based upon ability to meet mean liver dose (MLD, defined as liver-GTV) constraints; the 30 Gy threshold was the highest achievable. Of 7 eligible LRT plans, 5 with ablative 50 Gy peak doses were analyzed. Associated valley doses were 15 or 20 Gy. Median values of mean GTV and PTV doses for these plans were 36.2 (IQR, 34.6 - 37.8) and 32.9 (IQR, 31.3 - 33.4) Gy, respectively. A median of 12.4% (IQR, 7.4 - 28.4) of the GTV received a dose of 50 Gy. Median doses to 0.5 cc of stomach and duodenum were 16.7 Gy (range, 15.6 - 19.6) and 14.4 Gy (range, 12.3 - 23.9), respectively. The median value for MLD was 13.9 Gy (range, 13.6 to 14.8) and the median volume of normal liver spared 15 Gy was 1114 cm3 (range, 969 to 1154). These hepatic parameters were significantly decreased compared to a standard 30 Gy SBRT plan (18.1 Gy and 611.3 cc spared, p = 0.043 for both) which did not meet constraints. Dose escalation of advanced HCC using LRT is dosimetrically feasible. Though mean target doses remained limited by MLD, LRT allowed delivery of ablative dose to 12.4% of the GTV while meeting critical OAR constraints. Intratumoral dose-escalation may improve local control in advanced HCC patients.

Radiotherapy Dose as a Predictor of Outcomes Following Cardiac Radioablation for High-risk Refractory VT

Cardiac radioablation (CRA) is an emerging treatment for high-risk refractory ventricular tachycardia (VT). Despite a fixed prescription dose to the planning target volume (PTV) there is still considerable heterogeneity in the radiotherapy dose distribution due to planning technique, proximity to organs at risk, and radiation oncologist preference. The hypothesis is that plans with an inherently "hotter" internal dose to the PTV may lead to improved VT outcomes. Single-center, IRB-approved retrospective case series of patients with refractory VT who had failed at least one prior CA (or were unfit for CA) treated with CRA. All patients were treated with a single fraction of 25 Gy prescribed to the PTV. Maximum dose to PTV was collected from each plan and stratified as high vs low above and below the median. Maximum dose was defined as the highest dose delivered to the "hottest" 0.035 cc of the PTV to avoid known variability in reporting of dose to single voxels within the treatment planning system. Rates of survival (OS), freedom from shock and/or storm (FFSS), and freedom from death, shock, and/or storm (FFDSS) were collected, and stratified by maximum dose to the PTV. Formal statistical comparisons were not performed due to limited patient numbers. From 2015-2020, 22 patients were treated with CRA (18 with prior CA, 4 unfit for CA) for high-risk refractory VT. Median age was 64.5 years (range, 49-84), and 90.9% were male. 50% had ICM, with a median NYHA class of 3 (range, 1-4) and median EF of 25% (range, 15-58%). Median follow-up was 31.3 months. 2-year OS was 54.5%, FFSS was 42.4%, and FFDSS was 27.3%. Median maximum dose to the PTV was 42.2 Gy (range, 29.2-45.8 Gy). PTV maximum dose (high vs low) discriminated 2-year OS (63.6% vs 45.5%), FFSS (50% vs 30%) and FFDSS (36.4% vs 18.2%). For all endpoints, Kaplan-Meier curves overlapped for the first 6 months, and then diverged. In patients with high-risk refractory VT treated with CRA, survival and VT outcomes were similar between both groups out to 6 months, with improved OS and VT control noted after that with higher maximum doses. With a prescription dose of 25 Gy to the PTV, adjusting planning parameters to maintain maximum doses > 42 Gy may improve durable outcomes and requires validation in a larger cohort.

Automated VMAT treatment planning using sequential convex programming: algorithm development and clinical implementation

Objective. To develop and clinically implement a fully automated treatment planning system (TPS) for volumetric modulated arc therapy (VMAT). Approach. We solve two constrained optimization problems sequentially. The tumor coverage is maximized at the first step while respecting all maximum/mean dose clinical criteria. The second step further reduces the dose at the surrounding organs-at-risk as much as possible. Our algorithm optimizes the machine parameters (leaf positions and monitor units) directly and the resulting mathematical non-convexity is handled using the sequential convex programming by solving a series of convex approximation problems. We directly integrate two novel convex surrogate metrics to improve plan delivery efficiency and reduce plan complexity by promoting aperture shape regularity and neighboring aperture similarity. The entire workflow is automated using the Eclipse TPS application program interface scripting and provided to users as a plug-in, requiring the users to solely provide the contours and their preferred arcs. Our program provides the optimal machine parameters and does not utilize the Eclipse optimization engine, however, it utilizes the Eclipse final dose calculation engine. We have tested our program on 60 patients of different disease sites and prescriptions for stereotactic body radiotherapy (paraspinal (24 Gy × 1, 9 Gy × 3), oligometastis (9 Gy × 3), lung (18 Gy × 3, 12 Gy × 4)) and retrospectively compared the automated plans with the manual plans used for treatment. The program is currently deployed in our clinic and being used in our daily clinical routine to treat patients. Main results. The automated plans found dosimetrically comparable or superior to the manual plans. For paraspinal (24 Gy × 1), the automated plans especially improved tumor coverage (the average PTV (Planning Target Volume) 95% from 96% to 98% and CTV100% from 95% to 97%) and homogeneity (the average PTV maximum dose from 120% to 116%). For other sites/prescriptions, the automated plans especially improved the duty cycle (23%–39.4%). Significance. This work proposes a fully automated approach to the mathematically challenging VMAT problem. It also shows how the capabilities of the existing (Food and Drug Administration)FDA-approved commercial TPS can be enhanced using an in-house developed optimization algorithm that completely replaces the TPS optimization engine. The code and pertained models along with a sample dataset will be released on our ECHO-VMAT GitHub (https://github.com/PortPy-Project/ECHO-VMAT).

Dosimetric comparison and evaluation of two computational algorithms in VMAT treatment plans.

This study aimed to assess the accuracy and dosimetric impact of the Acuros XB (AXB) algorithm compared to the Anisotropic Analytical Algorithm (AAA) in two situations. First, simple phantom geometries were set and analyzed; moreover, volumetric modulated arc therapy (VMAT) clinical plans for Head & Neck and lung cases were calculated and compared. First, a phantom study was performed to compare the algorithms with radiochromic EBT3 film doses using one PMMA slab phantom and two others containing foam or air gap. Subsequently, a clinical study was conducted, including 20 Head & Neck and 15 lung cases irradiated with the VMAT technique. The treatment plans calculated by AXB and AAA were evaluated in terms of planning target volume (PTV) coverage (V95% ), dose received by relevant organs at risk (OARs), and the impact of using AXB with a grid size of 1mm. Finally, patient-specific quality assurance (PSQA) was performed and compared for 17 treatment plans. Phantom dose calculations showed a better agreement of AXB with the film measurements. In the clinical study, AXB plans exhibited lower Conformity Index and PTV V95% , higher maximum PTV dose, and lower mean and minimum PTV doses for all anatomical sites. The most notable differences were detected in regions of intense heterogeneity. AXB predicted lower doses for the OARs, while the calculation time with a grid size of 1mm was remarkably higher. Regarding PSQA, although AAA was found to exhibit slightly higher gamma passing rates, the difference did not affect the AXB treatment plan quality. AXB demonstrated higher accuracy than AAA in dose calculations of both phantom and clinical conditions, specifically in interface regions, making it suitable for sites with large heterogeneities. Hence, such dosimetric differences between the two algorithms should always be considered in clinical practice.

Dosimetric Study Comparing 3D Conformal Radiotherapy (3D-CRT), Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) in Hypofractionated One-Week Radiotherapy Regimen in Breast Cancer.

Introduction Recently, the one-week hypofractionated radiotherapy regimen (26 Gy in 5 fractions) for adjuvant breast radiotherapy has been shown to be non-inferior to other hypofractionated regimens (15-16 fractions). The aim of the present dosimetric study is to compare Intensity Modulated Radiotherapy (IMRT), Volumetric Modulated Arc Therapy (VMAT) and 3D Conformal Radiotherapy (3D-CRT) for a one-week hypofractionated radiotherapy regimen (26 Gy in 5 fractions) for adjuvant breast radiotherapy. Methods A total of 30 patients with histologically proven invasive carcinoma of the breast after breast conservation surgery (BCS) or modified radical mastectomy (MRM) were considered for in silico planning study. The dose prescription used was 26 Gy in 5 fractionsas used in the FAST Forward protocol. Targets were contoured according to standard guidelines. The heart, ipsilateral lung, and contralateral breast were contoured as organs at risk. Results Planning Target Volume (PTV) coverage:For IMRT, VMAT and 3D-CRT, respectively, the volumes that received at least 95% of the prescription dose (V95) were 95.7 ± 2.12, 92.47 ± 3.83, 90.87 ± 5.13; mean PTV doses (Dmean) were 26.1 ± 0.6, 25.7 ± 0.7, and 28 ± 4.39 (3D-CRT has higher Dmean compared to other techniques). Maximum PTV doses (Dmax) were 28.23 ± 0.72, 28.73 ± 0.64, and 29.8 ± 1.03. IMRT had a better V95 coverage and conformity index. Organs At Risk (OARs):The volumes that received at least 25% of the prescription dose (V25) of the heart were 3.41 ± 4.7, 1.8 ± 2.02 and 4.3 ± 6.98 in IMRT, VMAT and 3D-CRT, respectively. The volumetric (V25) comparison of heart dose in left-sided breast cancer was significantly different between VMAT and 3D-CRT (p=0.04, Wilcoxon signed-rank test). The volume that received at least 5% of the prescription dose (V5)was less than 25% in the 3D-CRT plan (12.55).For the ipsilateral lung, the V25 parameters were 19.53 ± 10.96, 23.93 ± 13.58 and 20.5 ± 12.32 in IMRT, VMAT and 3D-CRT, respectively. Conclusion From this study, we can conclude that IMRT and VMAT techniques are feasible and can achieve better dosimetric goals for target and OARs though minimizing the area achieving low dose remains to be a dosimetric concern for VMAT.

Dosimetric Evaluation of Physical Radiation Delivery Limits of a Weak Magnetic Field Generator on GBM Dose Distributions

<h3>Purpose/Objective(s)</h3> To demonstrate the feasibility of meeting dose prescription criteria when using a weak magnetic field generator to support glioblastoma multiforme (GBM) radiation therapy. <h3>Materials/Methods</h3> Weak magnetic fields extend free radical life, and recent experimental results have shown that adding weak magnetic fields (20G-40G) to radiation therapy delivery enhances free radical production, increases tumor cell death, and slows tumor growth. Based on these results, we have built the first clinical unit, consisting of two 63 cm ID Helmholtz coils, spaced 35 cm apart. The coil system is placed such that the patient and Linac couch are within the coils, and the Linac isocenter is coincident with the center of the coil system. We propose to use GBM for our first clinical trial. The limitation imposed by the coil system is a fixed Linac couch angle, constraining the gantry rotation to slightly more than 180°, from lateral to lateral. The impact on treatment plan quality of the corresponding reduction in available beam angles was unknown, so we conducted a treatment planning study to determine if we could provide clinically equivalent treatment plans with the coil in place. We evaluated the treatment plans for 10 GBM patients that had been treated with arc therapy. The prescription was 60 Gy (2 Gy x 30 fractions) for 6 patients, 55.8 Gy (1.8 Gy x 31 fractions) for 2 patients, 54 Gy (1.8 Gy x 30 fractions) for 1 patient, and 40.05 Gy (2.67 Gy x 15 fractions) for 1 patient. The dose was delivered to 95% of the planning target volume (PTV). The PTV margin was 1.3-2 cm surrounding the gross tumor volume. Critical structures, such as the brainstem, optic nerves, and optic chiasm, were contoured and assigned constraints of 62 Gy, 54 Gy, and 54 Gy, respectively. We repeated the treatment planning session using only coplanar arcs that spanned from 90° to 270° (half-arcs). <h3>Results</h3> All the treatment plans generated with the half-arcs met the clinical criteria. The minimum PTV doses for the half arc and clinical plans were 50.0 ± 6.1 Gy and 51.4 ± 7.1 Gy, and the maximum PTV doses were 61.9 ± 7.1 Gy and 62.7 ± 8.6 Gy, respectively. Table 1 summarizes the results of four reported critical structures. All the critical structures met the criteria, and the half-arc plans were neither better nor worse than the clinical plans. <h3>Conclusion</h3> The physical limits imposed by the magnetic field generator on the Linac beam angles do not degrade treatment planning for GBM radiation therapy. The prescribed dose can be adequately delivered while avoiding critical structures. With this groundwork, we can develop clinical trials to evaluate the impact of utilizing weak magnetic fields in radiation therapy.

Stereotactic Body Radiotherapy for Renal Cell Carcinoma: Oncological and Renal Function Outcomes

AimsTo evaluate oncological and renal function outcomes of stereotactic body radiotherapy (SBRT) for medically inoperable patients with localised renal cell carcinoma. Materials and methodsConsecutive patients treated with curative intent SBRT (30–45 Gy in five fractions or 42 Gy in three fractions) were included. Data on local control (Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), distant metastasis, impact on estimated glomerular filtration rate (eGFR) and proportional ipsilateral and contralateral renal functions (measured through renal scans) were collected. Univariate and multivariable analyses were conducted to determine association of variables with oncological and renal function outcomes. ResultsSeventy-four patients were analysed. The median follow-up was 27.8 months (interquartile range 17.6–41.7). Fifty-seven per cent had tumours ≥ T1b. One-, 2- and 4-year cumulative incidence of local failure was 5.85, 7.77 and 7.77%, respectively. The cumulative incidence of distant metastasis at 2 years was 4.24%. On multivariable analysis, a lower planning target volume (PTV) mean dose (P = 0.019) and a larger PTV (P = 0.005) were significantly associated with the risk of developing local failure. A lower PTV maximum dose (P = 0.039) was significantly associated with the risk of developing distant metastasis. The median change in global eGFR (ml/min) from pre-SBRT levels was –7.0 (interquartile range –14.5 to –1.0) at 1 year and –11.5 (interquartile range –19.5 to –4.0) at 2 years. The proportion of ipsilateral (differential) renal function decreased over time from 47% of overall renal function pre-SBRT to 36% at 2 years, whereas the proportion of contralateral renal function correspondingly improved. On multivariable analysis, a higher volume of uninvolved renal cortex (P < 0.0001) was significantly associated with a smaller decrease in eGFR over time. ConclusionIn this large institutional cohort, oncological outcomes of renal cell carcinoma treated with SBRT were favourable and a longitudinal decline in renal function in the ipsilateral kidney and compensatory increase in the contralateral kidney were observed. Clinical and dosimetric factors were significantly associated with oncological and renal function outcomes.

Feasibility and Short-Term Toxicity of a Consecutively Delivered Five Fraction Stereotactic Body Radiation Therapy Regimen in Early-Stage Breast Cancer Patients Receiving Partial Breast Irradiation.

BackgroundFor appropriately selected patients with early-stage breast cancer (ESBC), accelerated partial breast irradiation (APBI) yields equivalent rates of ipsilateral breast tumor recurrence with mixed results in patient-rated cosmesis compared with whole-breast radiotherapy depending on the technique utilized. When utilizing external beam radiotherapy for APBI, techniques to reduce target margins and overall treatment volume are potentially important to decrease rates of long-term adverse cosmesis. Stereotactic body radiotherapy (SBRT) is a promising technique to deliver APBI because of its increased accuracy and sparing of uninvolved breast tissue. We report the initial results of a prospective clinical trial investigating feasibility, safety, and cosmetic outcomes of a daily five-fraction SBRT regimen for APBI.MethodsTwenty-three patients with ESBC after lumpectomy who met APBI suitability were enrolled. During lumpectomy, a bioabsorbable three-dimensional fixed array tissue marker (BioZorb™, Hologic, Marlborough, MA) was placed for enhanced visualization of the cavity boundaries. Clinical target volume (CTV) was defined as the delineable cavity plus a 1-cm isotropic expansion followed by a 3-mm isotropic planning target volume (PTV) expansion. Patients received 30 Gy delivered in five planned consecutive daily fractions in either prone or supine positioning depending on individual anatomy. Two patients completed the five-fraction treatments in 9-day interval and 11-day interval due to external circumstances. A maximum PTV of 124cc was allowed to minimize incidence of fat necrosis. Plans utilized 10-MV flattening filter–free beams delivered on a Varian Edge linear accelerator. Local control, toxicity, and nurse/patient-scored cosmesis at pre-treatment baseline, 1 month post-treatment, and at subsequent 6-month intervals were recorded.ResultsTwenty-three patients were accrued at the time of submission with median follow-up of 6 months. No patients experienced grade ≥3 acute toxicity. Of the 10 events reported probably related to SBRT, nine were grade 1 (n = 9/10, 90%). There was no evidence of difference, deterioration, or change in patient or nurse-scored cosmesis from baseline to 1 and 6 months post-treatment. One patient developed nodal failure shortly after APBI.ConclusionsAlthough longer follow-up is needed to assess long-term toxicity and local control, this study demonstrated a five-fraction SBRT regimen delivered over consecutive days is a safe, efficient, well-tolerated, and cosmetically favorable means of delivering APBI in suitable women.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03643861, NCT03643861.

Abstract P3-19-18: Feasibility and short term toxicity of a consecutively delivered 5-fraction stereotactic body radiotherapy in early stage breast cancer patients receiving accelerated partial breast irradiation

Abstract Background: For early stage breast cancer, breast conservation is an appealing option for many women. Interest in reducing the duration and volume of RT has continued in the form of accelerated partial breast irradiation (APBI). Recent work demonstrates that for appropriately selected patients, APBI yields equivalent rates of ipsilateral breast tumor recurrence (IBTR) with improvements in patient rated cosmesis compared to whole breast radiotherapy. When using external beam radiotherapy for APBI, appropriate techniques to reduce setup uncertainty and overall treatment volume are critical to reduce long term adverse cosmesis. Stereotactic body radiotherapy (SBRT) is an attractive technique to deliver APBI because of its excellent accuracy and potentially superior sparing of uninvolved breast tissue. We report here the initial results of our IRB-approved prospective clinical trial investigating feasibility, safety, and cosmetic outcomes of daily, 5-fraction SBRT for APBI in women meeting ASTRO consensus suitability criteria for partial breast irradiation. Methods: We enrolled twenty patients with early stage breast cancer after lumpectomy who met APBI suitability. During lumpectomy, a breast surgeon placed a bioabsorbable 3D fixed array tissue marker (BioZorb™, Hologic, Marlborough, MS) for enhanced visualization of the cavity boundaries. We defined the clinical target volume (CTV) as the delineable cavity plus a 1 cm isotropic expansion. We placed a 3mm isotropic planning target volume (PTV) expansion around the CTV. We treated each woman with 3000cGy delivered in 5 consecutive, daily, free-breathed fractions in either prone or supine positioning depending on individual anatomy. Patient treatment position was free-breathing in the prone position for 17 patients and supine in 3 patients using triggered imaging and fiducial tracking. A maximum PTV of 124cc was allowed to minimize incidence of fat necrosis. Plans used 10MV flattening filter free (FFF) beams delivered on a Varian Edge linear accelerator. We documented the following: adverse events (CTCAE 4.0), causality of the event to SBRT, and nurse- and patient- scored cosmesis (i.e., 1=excellent, 2=good, 3=fair, 4=poor) at pre-treatment baseline, 1 month post-treatment, and at each proceeding 6 month interval. We also clinically surveilled for disease recurrence. Results: We completed accrual and treatment of twenty patients. At time of submission, fourteen patients had completed 6-month follow-up, and eight patients had completed 12-month follow-up. No patients experienced grade ≥3 toxicity. Adverse events reported were mostly grade 1. Eighty-five percent of patient-scored cosmesis were excellent or good at baseline, with no evidence of deterioration at 1-month post-treatment (Baseline = 1.9, 1 month = 1.9; p = 0.914). Eighty-five percent of nurse-scored cosmesis reports were excellent or good at baseline, with no evidence of deterioration between baseline and 1-month post-treatment (Baseline = 1.95, 1 month = 1.90; p = 0.564). Eighty-six percent of patients had excellent or good patient- and nurse-scored cosmesis at 6 months, with either mean score of 1.71. Eighty-eight percent of patients had excellent or good patient- and nurse-scored cosmesis at 12 months, with mean cosmesis score of 1.50 and 1.63, respectively. Local control follow-up is immature, but no patients developed IBTR. Conclusions: Our study demonstrated that consecutive daily 5-fraction breast SBRT for APBI is a safe, efficient, well-tolerated, and cosmetically favorable means of delivering partial breast irradiation in suitable women. As follow-up duration matures, we will report long term cosmetic outcome and recurrence. Citation Format: Yilan Liu, Christopher Veale, Diana Hablitz, Helen Krontiras, Michael Christian Dobelbower, Rachael Lancaster, Markus Bredel, Catherine Parker, Kimberly Keene, Evan Thomas, Drexell Hunter Boggs. Feasibility and short term toxicity of a consecutively delivered 5-fraction stereotactic body radiotherapy in early stage breast cancer patients receiving accelerated partial breast irradiation [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-18.

Cumulative Target Volume Dose and Locoregional Failure in Pancreatic Cancer Patients With Treated With Ablative Stereotactic MR-Guided Adaptive Radiation Therapy (SMART)

<h3>Purpose/Objective(s)</h3> Emerging data suggest that ablative stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) for inoperable pancreas cancer (PCa) achieves favorable local control (LC) and overall survival (OS) compared to non-ablative dose. In the current SMART workflow, each adaptive fraction is reoptimized without accounting for previously delivered dose. Cumulative target volume (TV) dose from all SMART fractions has not previously been evaluated with respect to clinical outcomes. <h3>Materials/Methods</h3> We evaluated 44 inoperable PCa patients who were prescribed 50 Gy in 5 daily fractions on a 0.35T-MR LINAC. 33 patients (75%) were treated with elective nodal irradiation, typically including the celiac axis and superior mesenteric artery. PTV margin was 3 mm. On-table adaptive replanning was performed to primarily satisfy gastrointestinal (GI) organ at risk (OAR) constraints, and secondarily maximize TV coverage. Cumulative dose for all fractions was summed onto a TRUFI MR fractional scan (i.e., fraction 5). A rigid transformation was performed for fractions 1 to 4 scans onto the fraction 5 frame of reference (FOR) based on alignment of gross disease. Each fractional dose was transformed onto fraction 5 FOR and summed cumulatively for all 5 fractions. Locoregional failure (LRF) was delineated on follow-up imaging by a diagnostic radiologist with PCa expertise. Cumulative TV dose metrics (D80, D90, mean, max) were evaluated with respect to LRF. Diagnostic scans were rigidly registered to the fraction 5 FOR based on recurrence region to investigate recurrence characteristics and target dose metrics. A Spearman correlation was used to investigate LRF and (1) ENI vs. no ENI, (2) TV coverage metrics, (3) planning TV (PTV) volume. <h3>Results</h3> The median PTV volume for all patients, with ENI, and without ENI was 125.9 cc (range: 20.6-356.8), 137.3 cc (range: 72.8-356.8, and 55.4 (range: 20.6-280.15), respectively. LRF occurred in 12 patients (27.3%); the median LRF volume was 10.9 cc (range: 1.1-145.5cc). The median Dice similarity coefficient taken to characterize LRF overlap with PTV was 0.05 (range: 0-0.45). Moderate negative correlation coefficients were noted between recurrence to ENI [-0.59 (<i>P</i> < 0.001)], recurrence to PTV volume [-0.41 (<i>P</i> < 0.001)] and recurrence to max PTV dose [–0.47 (<i>P</i> < 0.001)]. No correlation was observed for cumulative D80, D90, mean dose to recurrence. <h3>Conclusion</h3> To our knowledge, this is the first analysis of cumulative TV dose from 5-fraction SMART for PCa. While use of ENI is controversial, moderate and statistically significant correlations were noted between LRF and ENI, in addition to PTV volume and maximum dose. Additional investigation is warranted to better understand whether specific dose thresholds exist for gross disease and electively treated volumes with respect to long-term LC and OS.

A Dose-Response Model of Local Tumor Control Probability After Stereotactic Radiosurgery for Brain Metastases Resection Cavities

PurposeRecent randomized controlled trials evaluating stereotactic surgery (SRS) for resected brain metastases question the high rates of local control previously reported in retrospective studies. Tumor control probability (TCP) models were developed to quantify the relationship between radiation dose and local control after SRS for resected brain metastases. Methods and MaterialsPatients with resected brain metastases treated with SRS were evaluated retrospectively. Melanoma, sarcoma, and renal cell carcinoma were considered radio-resistant histologies. The planning target volume (PTV) was the region of enhancement on T1 post-gadolinium magnetic resonance imaging plus a 2-mm uniform margin. The primary outcome was local recurrence, defined as tumor progression within the resection cavity. Cox regression evaluated predictors of local recurrence. Dose-volume histograms for the PTV were obtained from treatment plans and converted to 3-fraction equivalent doses (α/β = 12 Gy). TCP models evaluated local control at 1-year follow-up as a logistic function of dose-volume histogram data. ResultsAmong 150 cavities, 41 (27.3%) were radio-resistant. The median PTV volume was 14.6 mL (range, 1.3-65.3). The median prescription was 21 Gy (range, 15-25) in 3 fractions (range, 1-5). Local control rates at 12 and 24 months were 86% and 82%. On Cox regression, larger cavities (PTV > 12 cm3) predicted increased risk of local recurrence (P = .03). TCP modeling demonstrated relationships between improved 1-year local control and higher radiation doses delivered to radio-resistant cavities. Maximum PTV doses of 30, 35, and 40 Gy predicted 78%, 89%, and 94% local control among all radio-resistant cavities, versus 69%, 79%, and 86% among larger radio-resistant cavities. ConclusionsAfter SRS for resected brain metastases, larger cavities are at greater risk of local recurrence. TCP models suggests that higher radiation doses may improve local control among cavities of radio-resistant histology. Given maximum tolerated doses established for single-fraction SRS, fractionated regimens may be required to optimize local control in large radio-resistant cavities.

Stereotactic body radiotherapy with a single isocentre for multiple pulmonary metastases

A 45-year-old male developed a second set of pulmonary metastases 5 years after surgery for extraskeletal mucinous chondrosarcoma of the left shoulder. He already underwent a lobectomy and two segmentectomies for a first set of pulmonary metastases 2 years ago. The closely grouped three nodules within the left lower lung formed a planning target volume (PTV) for stereotactic body radiotherapy (SBRT) with a single isocentre, which was focused on the centre of the largest nodule (the simultaneous plan). Dose-volume histogram analysis confirmed that the plan was superior to an alternative plan, in which SBRT plans would have been produced for each individual tumour (the individual plan). The mean, maximum and minimum PTV doses were 54.0, 57.5 and 47.3 Gy, respectively, in the simultaneous plan, and 65.6, 87.2 and 52.3 Gy, respectively, in the individual plan. The homogeneity index, conformity index, and the maximum dose delivered to the surrounding healthy lung were 1.21, 0.71, and 37.7 Gy, respectively, in the simultaneous plan and 1.66, 4.44, and 46.2 Gy, respectively, in the individual plan. The patient developed Grade two pneumonitis, but remained healthy until 4 years after the SBRT. When multiple closely grouped metastases are treated using SBRT, the use of a single isocentre should be considered.

Automated planning through robust templates and multicriterial optimization for lung VMAT SBRT of lung lesions

PurposeTo develop and validate a robust template for VMAT SBRT of lung lesions, using the multicriterial optimization (MCO) of a commercial treatment planning system.MethodsThe template was established and refined on 10 lung SBRT patients planned for 55 Gy/5 fr. To improve gradient and conformity a ring structure around the planning target volume (PTV) was set in the list of objectives. Ideal fluence optimization was conducted giving priority to organs at risk (OARs) and using the MCO, which further pushes OARs doses. Segmentation was conducted giving priority to PTV coverage. Two different templates were produced with different degrees of modulation, by setting the Fluence Smoothing parameter to Medium (MFS) and High (HFS).Each template was applied on 20 further patients. Automatic and manual plans were compared in terms of dosimetric parameters, delivery time, and complexity. Statistical significance of differences was evaluated using paired two‐sided Wilcoxon signed‐rank test.ResultsNo statistically significant differences in PTV coverage and maximum dose were observed, while an improvement was observed in gradient and conformity. A general improvement in dose to OARs was seen, which resulted to be significant for chest wall V30 Gy, total lung V20 Gy, and spinal cord D0.1 cc. MFS plans are characterized by a higher modulation and longer delivery time than manual plans. HFS plans have a modulation and a delivery time comparable to manual plans, but still present an advantage in terms of gradient.ConclusionThe automation of the planning process for lung SBRT using robust templates and MCO was demonstrated to be feasible and more efficient.

Dosimetric study for spine stereotactic body radiation therapy: magnetic resonance guided linear accelerator versus volumetric modulated arc therapy.

BackgroundStereotactic body radiation therapy (SBRT) given in 1-5 fractions is an effective treatment for vertebral metastases. Real-time magnetic resonance-guided radiotherapy (MRgRT) improves soft tissue contrast, which translates into accurate delivery of spine SBRT. Here we report on clinical implementation of MRgRT for spine SBRT, the quality of MRgRT plans compared to TrueBeam based volumetric modulated arc therapy (VMAT) plans in the treatment of spine metastases and benefits of MRgRT MR scan.Patients and methodsTen metastatic lesions were included in this study for plan comparison. Lesions were spread across thoracic spine and lumbosacral spine. Three fraction spine SBRT plans: 27Gy to planning target volume (PTV) and 30Gy to gross tumor volume (GTV) were generated on the ViewRay MRIdian Linac system and compared to TrueBeamTM STx based VMAT plans. Plans were compared using metrics such as minimum dose, maximum dose, mean dose, ratio of the dose to 50% of the volume (R50), conformity index, homogeneity index and dose to the spinal cord.ResultsMRIdian plans achieved equivalent target coverage and spinal cord dose compared to VMAT plans. The maximum and minimum PTV doses and homogeneity index were equivalent for both planning systems. R50 was lower for MRIdian plans compared to VMAT plans, indicating a lower spread of intermediate doses with MRIdian system (5.16 vs. 6.11, p = 0.03).ConclusionsMRgRT can deliver high-quality spine SBRT plans comparable to TrueBeam volumetric modulated arc therapy (VMAT) plans.

Comparison of the dose escalation potential for two hypofractionated radiotherapy regimens for locally advanced pancreatic cancer

ObjectivesTo determine the potential for dose escalation to a biological equivalent dose BED10≅100 Gy in hypofractionated radiotherapy for locally advanced pancreatic cancer (LAPC). Materials and methodsTen unselected LAPC patients were retrospectively included in the study. Two fractionation regimens were compared (5 and 15 fractions). The aim was to cover 95% of the Planning Target Volume (PTV) with a BED10 = 54 Gy (base dose = 33 Gy in 5 fractions, 42.5 Gy in 15 fractions) whilst respecting organs-at-risk (OAR) constraints. Once the highest PTV coverage was achieved dose escalation to a BED10≅100 Gy (escalated dose = 50 Gy in 5 fractions, 67.5 Gy in 15 fractions) was attempted, limiting the PTV maximum dose to 130% of the escalated dose. ResultsIn 5 fractions, 95% PTV coverage by both base and escalated doses could be achieved for one patient with PTV more than 1 cm away from OAR. 95% and 90% PTV coverage by the base dose was achieved in one and two patients respectively. In all other patients, coverage even by the base dose had to be compromised to comply with OAR constraints. In 15 fractions, 95% PTV coverage by the base dose was feasible for all patients except one. Dose escalation allowed improvement in target coverage by the base dose in both fractionation regimen whilst covering a sub-volume of the PTV with a BED10≅100 Gy. Both fractionation schemes were equivalent in terms of dose escalation potential. ConclusionLAPC patients with OAR close to the PTV are generally not eligible for hypofractionation with dose escalation. However, this planning study shows that it is possible to cover PTV sub-volumes with a BED10≅100 Gy in addition to delivering a BED10 = 54 Gy to 90–95% of the PTV as commonly prescribed to this population. Combined with an adaptive approach, this may maximize PTV coverage by a high BED on days with favourable anatomy.

Clinical Results of Mean GTV Dose Optimized Robotic-Guided Stereotactic Body Radiation Therapy for Lung Tumors.

We retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean dose optimized stereotactic body radiation therapy (SBRT) for primary and secondary lung tumors with and without robotic real-time motion compensation. Between 2011 and 2017, 208 patients were treated with SBRT for 111 primary lung tumors and 163 lung metastases with a median GTV of 8.2 cc (0.3-174.0 cc). Monte Carlo dose optimization was performed prioritizing GTV mean dose at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The median GTV mean biological effective dose (BED)10 was 162.0 Gy10 (34.2-253.6 Gy10) and the prescribed PTV BED10 ranged 23.6-151.2 Gy10 (median, 100.8 Gy10). Motion compensation was realized through direct tracking (44.9%), fiducial tracking (4.4%), and internal target volume (ITV) concepts with small (≤5 mm, 33.2%) or large (>5 mm, 17.5%) motion. The local control (LC), progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. Median follow-up was 14.5 months (1-72 months). The 2-year actuarial LC, PFS, and OS rates were 93.1, 43.2, and 62.4%, and the median PFS and OS were 18.0 and 39.8 months, respectively. In univariate analysis, prior local irradiation (hazard ratio (HR) 0.18, confidence interval (CI) 0.05-0.63, p = 0.01), GTV/PTV (HR 1.01-1.02, CI 1.01-1.04, p < 0.02), and PTV prescription, mean GTV, and maximum plan BED10 (HR 0.97-0.99, CI 0.96-0.99, p < 0.01) were predictive for LC while the tracking method was not (p = 0.97). For PFS and OS, multivariate analysis showed Karnofsky Index (p < 0.01) and tumor stage (p ≤ 0.02) to be significant factors for outcome prediction. Late radiation pneumonitis or chronic rip fractures grade 1-2 were observed in 5.3% of the patients. Grade ≥3 side effects did not occur. Robotic SBRT is a safe and effective treatment for lung tumors. Reducing the PTV prescription and keeping high GTV mean doses allowed the reduction of toxicity while maintaining high local tumor control. The use of real-time motion compensation is strongly advised, however, well-performed ITV motion compensation may be used alternatively when direct tracking is not feasible.

Fine-tuning the normal tissue objective in eclipse for lung stereotactic body radiation therapy

The purpose of this study was to characterize the effects of the normal tissue objective (NTO) on lung stereotactic body radiation therapy (SBRT) dose distributions. The NTO is a spatially varying constraint used in Eclipse to limit dose to normal tissues by steepening the dose gradient. However, the multitude of potential NTO setting combinations challenges optimal NTO tuning. In the present study, a broad range of NTO settings are investigated for lung SBRT treatment planning with volumetric modulated arc therapy(VMAT). Ten prior lung SBRT cases were replanned using NTO priorities of 1, 50, 100, 200, 500, and 999 in combination with fall-off values of 0.01, 0.05, 0.10, 0.15, 0.20, 0.30, 0.50, 1.00, and 5.00 mm−1 and the automatic NTO. NTO distances to planning target volume (PTV), start dose, and end dose were 1 mm, 100%, and 10%, respectively, for all 600 plans. Prescription dose covered 95% of the PTV. The following metrics were recorded: conformity index (CI), ratio of the 50% prescription isodose volume to PTV (R50%), maximum dose 2 cm away from PTV (D2cm), lung volume of ≥20 Gy (V20Gy), maximum PTV dose (PTVmax), and monitor units (MUs). Differences between prior plans and NTO plans were evaluated using the Wilcoxon signed-rank test. Different combinations of NTO settings resulted in wide-ranging plan quality metrics: CI (1.00 to 1.54), R50% (3.95 to 7.57), D2cm (33.4% to 67.9%), V20Gy (1.66% to 2.75%), MU (1.81 cGy−1 to 4.69 cGy−1), and PTVmax (118% to 175%). Although no settings were optimal for all metrics, a fall-off of 0.15 mm−1 and a priority of 500 best satisfied institutional criteria. Compared with prior plans, NTO plans resulted in significantly lower R50% (4.00 vs 4.35, p = 0.002), lower V20Gy (1.22% vs 1.32%, p = 0.006), and higher PTVmax (138% vs 122%, p = 0.002). All of the prior and well-tuned NTO plans met Radiation Therapy Oncology Group (RTOG) 0813 guidelines. Lung SBRT dose distributions were characterized across a range of NTO settings. NTO plans with well-tuned settings compared favorably with prior plans.