Mean Organs At Risk Doses Research Articles

Dosimetric impact of bone marrow sparing for robustly optimized IMPT for locally advanced cervical cancer

Background and purposeTo investigate the trade-off between bone marrow sparing (BMS) and dose to organs at risk (OARs) for intensity modulated proton therapy (IMPT) for women with locally advanced cervical cancer (LACC). Materials and methodsTwenty LACC patients were retrospectively included. IMPT plans were created for each patient using automated treatment planning. These plans progressively reduced bone marrow mean doses by steps of 1 GyRBE, while constraining target coverage and conformality. The relation between bone marrow dose and bladder, small bowel, rectum, and sigmoid doses was evaluated. ResultsA total of 140 IMPT plans were created. Plans without BMS had an average [range] bone marrow mean dose of 17.3 [14.7–21.6] GyRBE , which reduced to 12.0 [10.0–14.0] GyRBE with maximum BMS. The mean OAR dose [range] increased modestly for 1 GyRBE BMS: 0.2 [0.0 – 0.6] GyRBE for bladder, 0.3 [-0.2 – 0.7] GyRBE for rectum, 0.4 [0.1 – 0.8] GyRBE for small bowel, and 0.2 [-0.2 – 0.4] GyRBE for sigmoid. Moreover, for maximum BMS, mean OAR doses [range] escalated by 3.3 [0.1 – 6.7] GyRBE for bladder, 5.8 [1.8 – 12.4] GyRBE for rectum, 3.9 [1.6 – 5.9] GyRBE for small bowel, and 2.7 [0.6 – 5.9] GyRBE for sigmoid. ConclusionAchieving 1 GyRBE BMS for IMPT is feasible for LACC patients with limited dosimetric impact on other OARs. While further bone marrow dose reduction is possible for some patients, it may increase OAR doses substantially for others. Hence, we recommend a personalized approach when introducing BMS into clinical IMPT treatment planning to carefully assess individual patient benefits and risks.

Radiation Therapy for Stage IIA/B Seminoma: Modeling Secondary Cancer Risk for Protons and VMAT versus 3D Photons.

Radiation therapy (RT) is an effective treatment for stage IIA and select stage IIB seminomas. However, given the long life expectancy of seminoma patients, there are concerns about the risk of secondary cancers from RT. This study assessed differences in secondary cancer risk for stage II seminoma patients following proton pencil-beam scanning (PBS) and photon VMAT, compared to 3D conformal photon RT. Ten seminoma patients, five with a IIA staging who received 30 GyRBE and five with a IIB staging who received 36 GyRBE, had three RT plans generated. Doses to organs at risk (OAR) were evaluated, and secondary cancer risks were calculated as the Excess Absolute Risk (EAR) and Lifetime Attributable Risk (LAR). PBS reduced the mean OAR dose by 60% on average compared to 3D, and reduced the EAR and LAR for all OAR, with the greatest reductions seen for the bowel, liver, and stomach. VMAT reduced high doses but increased the low-dose bath, leading to an increased EAR and LAR for some OAR. PBS provided superior dosimetric sparing of OAR compared to 3D and VMAT in stage II seminoma cases, with models demonstrating that this may reduce secondary cancer risk. Therefore, proton therapy shows the potential to reduce acute and late side effects of RT for this population.

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

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

Is iodine-125 seed strand brachytherapy suitable for ureteral carcinoma?

Long-term conventional high-dose radiation therapy can lead to retroperitoneal fibrosis and nerve damage in patients with advanced ureteral carcinoma (UC). The purpose of this study is to evaluate the safety and efficacy of nephrostomy combined with iodine-125 seed strand (ISS) brachytherapy for the treatment of UC. Twenty-one patients with UC were treated with nephrostomy combined with ISS brachytherapy. The following parameters were recorded: technical success rate, procedure time, complications, mean D90 (dose delivered to the 90% gross tumor volume), organ at risk (OAR) dose, local control rate (LCR), ureteral patency (UP), local tumor progression (LTP), and overall survival (OS). The hydronephrosis score (HS), visual analog score (VAS), Karnofsky score and maximum diameter (MD) were compared before and 8 weeks after the operation. The technical success rate was 100%, with a mean procedure time of 54.6 min. Three cases (14.5%) had bladder implant metastasis but no other major complications, such as ureteral perforation, infection, or severe bleeding, occurred. The mean D90 and OAR doses were 50.7 and 3.8 Gy, respectively. LCR was 100% with 28.6% UP at the 8-week evaluation. During the mean follow-up of 16.6 months, LTP occurred in 4 cases (19.1%), and the median OS was 25.0 months (95% CI 21.3-28.5). The HS, VAS, Karnofsky score and MD showed significant changes (all P < 0.01). UC can be safely and effectively treated by nephrostomy combined with ISS brachytherapy, a viable option for patients who cannot undergo or refuse surgical resection.

Case study of a bolus helmet used to maintain optic chiasm and nerve sparing while improving target coverage using IMPT.

The purpose of this study was to examine if the use of a bolus helmet when treating the head with intensity modulated proton therapy (IMPT) will maintain organs at risk (OAR) sparing while improving the clinical target volume (CTV) coverage. A bolus helmet is a device that aims to improve on the traditionally used range shifter in proton therapy by improving dose distribution characteristics. Ten patients were retrospectively selected who had 2 separate treatment planning scans performed, a scan with the bolus helmet and a second scan without. Plans were created using both scans. Dose to organs at risk (OAR) including the left optic nerve, right optic nerve, optic chiasm, and normal brain minus CTV (brain-CTV), as well as CTV coverage were compared between the 2 plans. The use of the bolus helmet displayed lower mean OAR doses as well as higher CTV coverage, suggesting that use of the bolus helmet provides benefit when treating the head with IMPT.

The predictive value of segmentation metrics on dosimetry in organs at risk of the brain

BackgroundFully automatic medical image segmentation has been a long pursuit in radiotherapy (RT). Recent developments involving deep learning show promising results yielding consistent and time efficient contours. In order to train and validate these systems, several geometric based metrics, such as Dice Similarity Coefficient (DSC), Hausdorff, and other related metrics are currently the standard in automated medical image segmentation challenges. However, the relevance of these metrics in RT is questionable. The quality of automated segmentation results needs to reflect clinical relevant treatment outcomes, such as dosimetry and related tumor control and toxicity. In this study, we present results investigating the correlation between popular geometric segmentation metrics and dose parameters for Organs-At-Risk (OAR) in brain tumor patients, and investigate properties that might be predictive for dose changes in brain radiotherapy. MethodsA retrospective database of glioblastoma multiforme patients was stratified for planning difficulty, from which 12 cases were selected and reference sets of OARs and radiation targets were defined. In order to assess the relation between segmentation quality -as measured by standard segmentation assessment metrics- and quality of RT plans, clinically realistic, yet alternative contours for each OAR of the selected cases were obtained through three methods: (i) Manual contours by two additional human raters. (ii) Realistic manual manipulations of reference contours. (iii) Through deep learning based segmentation results. On the reference structure set a reference plan was generated that was re-optimized for each corresponding alternative contour set. The correlation between segmentation metrics, and dosimetric changes was obtained and analyzed for each OAR, by means of the mean dose and maximum dose to 1% of the volume (Dmax 1%). Furthermore, we conducted specific experiments to investigate the dosimetric effect of alternative OAR contours with respect to the proximity to the target, size, particular shape and relative location to the target. ResultsWe found a low correlation between the DSC, reflecting the alternative OAR contours, and dosimetric changes. The Pearson correlation coefficient between the mean OAR dose effect and the Dice was -0.11. For Dmax 1%, we found a correlation of -0.13. Similar low correlations were found for 22 other segmentation metrics. The organ based analysis showed that there is a better correlation for the larger OARs (i.e. brainstem and eyes) as for the smaller OARs (i.e. optic nerves and chiasm). Furthermore, we found that proximity to the target does not make contour variations more susceptible to the dose effect. However, the direction of the contour variation with respect to the relative location of the target seems to have a strong correlation with the dose effect. ConclusionsThis study shows a low correlation between segmentation metrics and dosimetric changes for OARs in brain tumor patients. Results suggest that the current metrics for image segmentation in RT, as well as deep learning systems employing such metrics, need to be revisited towards clinically oriented metrics that better reflect how segmentation quality affects dose distribution and related tumor control and toxicity.

Neoadjuvant Chemotherapy and Whole Ventricular Irradiation for Pure Intracranial Germinoma: A Comparison of Three Brain-Sparing Techniques.

ObjectiveTo quantitate and compare the dosimetric properties of three brain-sparing radiation therapy techniques for pure intracranial germinomas with dose-volume analysis of target and normal brain structures.MethodsWe identified 18 patients with central nervous system (CNS) germinoma who had achieved local control and had excellent neurocognitive outcomes. Four patients who were treated with a simultaneous integrated boost (SIB) plan of 22.5Gy to whole ventricle (WV) and 30Gy to primary were re-planned with 24Gy to WV-only and the Children’s Oncology Group (COG) protocol of 18Gy to WV with a sequential boost to 30Gy. Organ-at-risk (OAR) doses for hippocampi, temporal lobes, whole brain, whole brain minus whole ventricles planning target volume (WB-WVPTV), WVPTV, and boost volume were comparatively studied.ResultsFor patients treated with the SIB plan, an excellent neurocognitive function has previously been shown to be well preserved. Three-year event-free survival (EFS) and overall survival (OS) for this group have also previously been demonstrated (89.5% and 100%, respectively). Mean and integral OAR doses were comparable between SIB and WV-only plans but were lower for COG plans. Whole brain, whole brain minus WVPTV, and temporal lobe V20, V18, and V12, as well as hippocampi V20, V25, and V30, were comparable between SIB and WV-only plans but were lower for the COG plans.ConclusionCompared to the WV-only method, the SIB plan permits more dose to the primary site by 6 Gy without compromising neurocognitive control. While maintaining the 30Gy boost, the COG protocol reduces the WVPTV dose to 18Gy. It remains to be seen whether WV dose reduction risks reducing local control.

Characterization of knowledge-based volumetric modulated arc therapy plans created by three different institutions' models for prostate cancer.

The aim of this study was to clarify factors predicting the performance of knowledge-based planning (KBP) models in volume modulated arc therapy for prostate cancer in terms of sparing the organ at risk (OAR). In three institutions, each KBP model was trained by more than 20 library plans (LP) per model. To validate the characterization of each KBP model, 45 validation plans (VP) were calculated by the KBP system. The ratios of overlap between the OAR volume and the planning target volume (PTV) to the whole organ volume (Voverlap/Vwhole) were analyzed for each LP and VP. Regression lines between dose-volume parameters (V90, V75, and V50) and Voverlap/Vwhole were evaluated. The mean OAR dose, V90, V75, and V50 of LP did not necessarily match those of VP. In both the rectum and bladder, the dose-volume parameters for VP were strongly correlated with Voverlap/Vwhole at institutes A, B, and C (R > 0.74, 0.85, and 0.56, respectively). Except in the rectum at institute B, the slopes of the regression lines for LP corresponded to those for VP. For dose-volume parameters for the rectum, the ratios of slopes of the regression lines in VP to those in LP ranged 0.51-1.26. In the bladder, most ratios were less than 1.0 (mean: 0.77). For each OAR, each model made distinct dosimetric characterizations in terms of Voverlap/Vwhole. The relationship between dose-volume parameters and Voverlap/Vwhole of OARs in LP predicts the KBP models' performance sparing OARs.

Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?

Background The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. Material and methods Treatment plans (n = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. Results IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2–3.4 Gy (median: 1.9 Gy) in FB and 0.0–1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2–2.4% in FB and 0.0–1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0–1.5% and 0–2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0–2.2%). Conclusion According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.

Simultaneous integrated boost with helical arc radiotherapy of total skin (HEARTS) to treat cutaneous manifestations of advanced, therapy-refractory cutaneous lymphoma and leukemia - dosimetry comparison of different regimens and clinical application

BackgroundHelical irradiation of the total skin (HITS) was modified as simultaneous integrated boost (SIB)-helical arc radiotherapy of total skin (HEARTS) technique and applied to an acute myeloid leukemia (AML) patient with disseminated leukemia cutis.MethodsThe original HITS plan was revised for different regimens, i.e. HEARTS, low-dose HEARTS and SIB-HEARTS. The uniformity index (UI), conformity index (CI), and dose of organs at risk (OARs) were used to evaluate the plans. Additionally, the SIB-HEART (21/15 Gy) was delivered to the total skin and chloromas.ResultsNo significant differences were observed for the CI and UI between HITS and HEARTS regimens. Compared with HITS, the reduced mean doses to various bone marrows ranged from 17 to 88%. The mean OARs doses for the head, chest and abdomen of a patient with AML treated with SIB-HEARTS (21/15 Gy) were 2.1 to 21.9 Gy, 1.8 to 7.8 Gy and 1.7 to 3.3 Gy, respectively. No severe adverse effects were noted except for grade 4 leukocytopenia and thrombocytopenia.ConclusionHEARTS and different regimens reduced the dose to OARs and bone marrow while maintaining the uniformity and conformity. SIB-HEARTS deliveries different doses to the total skin and enlarged tumors simultaneously.Trial registrationRetrospectively registered and approved by the Institutional Review Board of our hospital (FEMH-106151-C).

Automated Knowledge-Based Intensity-Modulated Proton Planning: An International Multicenter Benchmarking Study.

Background: Radiotherapy treatment planning is increasingly automated and knowledge-based planning has been shown to match and sometimes improve upon manual clinical plans, with increased consistency and efficiency. In this study, we benchmarked a novel prototype knowledge-based intensity-modulated proton therapy (IMPT) planning solution, against three international proton centers. Methods: A model library was constructed, comprising 50 head and neck cancer (HNC) manual IMPT plans from a single center. Three external-centers each provided seven manual benchmark IMPT plans. A knowledge-based plan (KBP) using a standard beam arrangement for each patient was compared with the benchmark plan on the basis of planning target volume (PTV) coverage and homogeneity and mean organ-at-risk (OAR) dose. Results: PTV coverage and homogeneity of KBPs and benchmark plans were comparable. KBP mean OAR dose was lower in 32/54, 45/48 and 38/53 OARs from center-A, -B and -C, with 23/32, 38/45 and 23/38 being >2 Gy improvements, respectively. In isolated cases the standard beam arrangement or an OAR not being included in the model or being contoured differently, led to higher individual KBP OAR doses. Generating a KBP typically required <10 min. Conclusions: A knowledge-based IMPT planning solution using a single-center model could efficiently generate plans of comparable quality to manual HNC IMPT plans from centers with differing planning aims. Occasional higher KBP OAR doses highlight the need for beam angle optimization and manual review of KBPs. The solution furthermore demonstrated the potential for robust optimization.

Analysis of EORTC-1219-DAHANCA-29 trial plans demonstrates the potential of knowledge-based planning to provide patient-specific treatment plan quality assurance

IntroductionRadiotherapy treatment plan quality can influence clinical trial outcomes and general QA may not identify suboptimal organ-at-risk (OAR) sparing. We retrospectively performed patient-specific quality assurance (QA) of 100 head-and-neck cancer (HNC) plans from the EORTC-1219-DAHANCA-29 study. Materials and methodsA 177-patient RapidPlan (Varian Medical Systems) model comprising institutional HNC plans was used to QA trial plans (Ptrial). RapidPlan plans (Prapidplan) were created using RapidPlan and Eclipse scripting to achieve a high degree of automation. Comparison between Prapidplan mean predicted/achieved OAR doses, and Ptrial mean OAR doses was made for parotid/submandibular glands (PGs/SMGs) and swallowing muscles (SM). ResultsOAR predictions were made within 2 min per patient. Averaged PG/SMG/SM mean doses were 2.0/9.0/3.8 Gy lower in Prapidplan. Using predicted Prapidplan combined mean OAR dose as the benchmark, a total of 60/27/4 trial plans could be improved by 3/6/9 Gy respectively. DiscussionIndividualized QA indicated that OAR sparing could frequently be improved in EORTC-1219 study plans, even though they met the trial’s generic plan criteria. Automated, patient-specific QA can be performed within a few minutes and should be considered to reduce the influence of planning variation on trial outcomes.

Direction modulated brachytherapy (DMBT) for treatment of cervical cancer: A planning study with 192 Ir, 60 Co, and 169 Yb HDR sources.

To evaluate plan quality of a novel MRI-compatible direction modulated brachytherapy (DMBT) tandem applicator using 192 Ir, 60 Co, and 169 Yb HDR brachytherapy sources, for various cervical cancer high-risk clinical target volumes (CTVHR ). The novel DMBT tandem applicator has six peripheral grooves of 1.3-mm diameter along a 5.4-mm thick nonmagnetic tungsten alloy rod. Monte Carlo (MC) simulations were used to benchmark the dosimetric parameters of the 192 Ir, 60 Co, and 169 Yb HDR sources in a water phantom against the literature data. 45 clinical cases that were treated using conventional tandem-and-ring applicators with 192 Ir source (192 Ir-T&R) were selected consecutively from intErnational MRI-guided BRAchytherapy in CErvical cancer (EMBRACE) trial. Then, for each clinical case, 3D dose distribution of each source inside the DMBT and conventional applicators were calculated and imported onto an in-house developed inverse planning optimization code to generate optimal plans. All plans generated by the DMBT tandem-and-ring (DMBT T&R) from all three sources were compared to the respective 192 Ir-T&R plans. For consistency, all plans were normalized to the same CTVHR D90 achieved in clinical plans. The D2cm3 for organs at risk (OAR) such as bladder, rectum, and sigmoid, and D90, D98, D10, V100, and V200 for CTVHR were calculated. In general, plan quality significantly improved when a conventional tandem (Con.T) is replaced with the DMBT tandem. The target coverage metrics were similar across 192 Ir-T&R and DMBT T&R plans with all three sources (P>0.093). 60 Co-DMBT T&R generated greater hot spots and less dose homogeneity in the target volumes compared with the 192 Ir- and 169 Yb-DMBT T&R plans. Mean OAR doses in the DMBT T&R plans were significantly smaller (P<0.0084) than the 192 Ir-T&R plans. Mean bladder D2cm3 was reduced by 4.07%, 4.15%, and 5.13%, for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. Mean rectum (sigmoid) D2cm3 was reduced by 3.17% (3.63%), 2.57% (3.96%), and 4.65% (4.34%) for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. The DMBT T&R plans with the 169 Yb source generally resulted in the greatest OAR sparing when the CTVHR were larger and irregular in shape, while for smaller and regularly shaped CTVHR (<30cm3 ), OAR sparing between the sources were comparable. The DMBT tandem provides a promising alternative to the Con.T design with significant improvement in the plan quality for various target volumes. The DMBT T&R plans generated with the three sources of varying energies generated superior plans compared to the conventional T&R applicators. Plans generated with the 169 Yb-DMBT T&R produced best results for larger and irregularly shaped CTVHR in terms of OAR sparing. Thus, this study suggests that the combination of the DMBT tandem applicator with varying energy sources can work synergistically to generate improved plans for cervical cancer brachytherapy.

A Feasibility Study: Can the Dose to Recurrent Sacral Chordoma be Safely Escalated to 84.6Gy (RBE) Using Pencil-Beam-Scanning Proton Therapy and Volumetric-Modulated Arc Therapy?

Chordomas locally recurrent after surgery are difficult to control. Increasing the total radiation dose has the potential of increasing local control. We investigated the feasibility of dose escalation (84.6Gy RBE, 1.8Gy RBE/fraction) to the gross-tumor-volume (GTV) for recurrent chordomas while respecting dose constraints to organs-at-risk (OARs) using different pencil beam scanning (PBS) beam spot sizes and beam angles as well as VMAT planning. Several patients with recurrent sacral chordomas were selected retrospectively. These patients were originally treated at our institution with pre-operative RT with 50.4Gy RBE, followed by surgery and post-operative boost of 21.6Gy RBE. In this study, GTV is contoured on the recurrent CT image. Treatment plans were generated to provide dose escalation (84.6Gy RBE) to the recurrent GTV with a 3 mm margin. PBS plans were generated using intensity-modulated proton therapy (IMPT) with two sets of beams: one with posterior-anterior (PA) only, and the other with a left- and a right-posterior-oblique beam (LP and RP). Two different spot sizes were evaluated: 8 mm to 15 mm sigma versus 2.3 mm to 4.4 mm sigma in air at isocenter with energies from 220 MeV to 90 MeV. VMAT plans used four partial arcs. OAR dose constraints are listed in the Table and used as optimization objectives and constraints for IMPT and VMAT. The use of posterior-oblique beams reduced the maximum and mean dose to small bowel and bladder compared to a single PA beam. PBS (spot size of 2.3 mm to 4.4 mm) provided the best mean and maximum dose to OARs and improved GTV coverage. Neither PBS with PA beam using spot size of 8 mm to 15 mm, nor the VMAT, plans met the maximum dose constraints for bladder, small bowel and skin. Intergluteal-fold dose was lower with two posterior-oblique beams. VMAT plans had similar maximum and mean dose to some OARs compared to spot size of 8 mm to 15 mm. High dose radiation (84.6Gy RBE) can be delivered to GTV while respecting dose constraints to OARs with PBS using spot size of 2.3 mm to 4.4 mm. PBS generally provides lower mean OARs dose compared to VMAT. Institutions with larger spot size should compare PBS and VMAT plans with different PBS beam angles for certain OARs. Institutions with smaller spot size, two posterior-oblique beams may be favorable compared to a single PA beam.Abstract 3762Maximum dose (Gy RBE)OAR dose constraintsPBS-PA 8 mm-15 mmPBS-PA 2.3 mm-4.4 mmPBS-LP-RP 8 mm-15 mmPBS-LP-RP 2.3 mm-4.4 mmVMATGTV84.987.687.687.587.589.0Sigmoid77.467.066.866.866.465.7Bladder60.066.752.928.635.665.3Small Bowel57.66457.157.955.265.8Rectum77.476.170.977.768.772.7Cauda77.424.10.529.31.23.9Skin rim6674.174.065.262.389.1Mean dose (Gy RBE)PBS-PA 8 mm-15 mmPBS-PA 2.3 mm-4.4 mmPBS-LP-RP 8 mm-15 mmPBS-LP-RP 2.3 mm-4.4 mmVMATGTV85.78685.786.285.7Sigmoid21.015.619.29.821.6Bladder5.04.60.30.319.8Small Bowel2.53.61.20.89.5Rectum29.112.331.214.430.4Cauda2.80.04.70.11.9Skin rim4.57.55.83.44.4 Open table in a new tab

A method for a priori estimation of best feasible DVH for organs-at-risk: Validation for head and neck VMAT planning.

Despite improvements in optimization and automation algorithms, the quality of radiation treatment plans still varies dramatically. A tool that allows a priori estimation of the best possible sparing (Feasibility DVH, or FDVH) of an organ at risk (OAR) in high-energy photon planning may help reduce plan quality variability by deriving patient-specific OAR goals prior to optimization. Such a tool may be useful for (a) meaningfully evaluating patient-specific plan quality and (b) supplying best theoretically achievable DVH goals, thus pushing the solution toward automatic Pareto optimality. This work introduces such a tool and validates it for clinical Head and Neck (HN) datasets. To compute FDVH, first the targets are assigned uniform prescription doses, with no reference to any particular beam arrangement. A benchmark 3D dose built outside the targets is estimated using a series of energy-specific dose spread calculations reflecting observed properties of radiation distribution in media. For the patient, the calculation is performed on the heterogeneous dataset, taking into account the high- (penumbra driven) and low- (PDD and scatter-driven) gradient dose spreading. The former is driven mostly by target dose and surface shape, while the latter adds the dependence on target volume. This benchmark dose is used to produce the "best possible sparing" FDVH for an OAR, and based on it, progressively more easily achievable FDVH curves can be estimated. Validation was performed using test cylindrical geometries as well as 10 clinical HN datasets. For HN, VMAT plans were prepared with objectives of covering the primary and the secondary (bilateral elective neck) PTVs while addressing only one OAR at a time, with the goal of maximum sparing. The OARs were each parotid, the larynx, and the inferior pharyngeal constrictor. The difference in mean OAR doses was computed for the achieved vs. FDVHs, and the shapes of those DVHs were compared by means of the Dice similarity coefficient (DSC). For all individually optimized HN OARs (N = 38), the average DSC between the planned DVHs and the FDVHs was 0.961 ± 0.018 (95% CI 0.955-0.967), with the corresponding average of mean OAR dose differences of 1.8 ± 5.8% (CI -0.1-3.6%). For realistic plans the achieved DVHs run no lower than the FDVHs, except when target coverage is compromised at the target/OAR interface. For the validation of VMAT plans, the OAR DVHs optimized one-at-a-time were similar in shape to and bound on the low side by the FDVHs, within the confines of planner's ability to precisely cover the target(s) with the prescription dose(s). The method is best suited for the OARs close to the target. This approach is fundamentally different from "knowledge-based planning" because it is (a) independent of the treatment plan and prior experience, and (b) it approximates, from nearly first principles, the lowest possible boundary of the OAR DVH, but not necessarily its actual shape in the presence of competing OAR sparing and target dose homogeneity objectives.

Very high-energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS.

The aim of this study was to evaluate the performance of very high-energy electron beams (VHEE) in comparison to clinically derived treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PPBS) technology. We developed a custom optimization script that could be applied automatically across modalities to eliminate operator bias during IMRT optimization. Four clinical cases were selected (prostate cancer, lung cancer, pediatric brain tumor, and head and neck cancer (HNC)). The VHEE beams were calculated in the EGSnrc/DOSXYZnrc Monte Carlo code for 100 and 200MeV beams. Treatment plans with VHEE, VMAT, and PPBS were optimized in a research version of RayStation using an in-house developed script to minimize operator bias between the different techniques. The in-house developed script generated similar or superior plans to the clinically used plans. In the comparisons between the modalities, the integral dose was lowest for the PPBS-generated plans in all cases. For the prostate case, the 200MeV VHEE plan showed reduced integral dose and reduced organ at risk (OAR) dose compared to the VMAT plan. For all other cases, both the 100 and the 200MeV VHEE plans were superior to the VMAT plans, and the VHEE plans showed better conformity and lower spinal cord dose in the pediatric brain case and lower brain stem dose in the HNC case when compared to the PPBS plan. The automated optimization developed in this study generated similar or superior plans as compared to the clinically used plan and represents an unbiased approach to compare treatment plans generated for different modalities. In the present study, we also show that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases, and VHEE plans can even achieve reductions in OAR doses compared to PPBS plans for shallow targets. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses are achieved. On the whole, VHEE was intermediate between photon VMAT and PPBS for OAR sparing.

Using a knowledge-based planning solution to select patients for proton therapy

Background and purposePatient selection for proton therapy by comparing proton/photon treatment plans is time-consuming and prone to bias. RapidPlan™, a knowledge-based-planning solution, uses plan-libraries to model and predict organ-at-risk (OAR) dose-volume-histograms (DVHs). We investigated whether RapidPlan, utilizing an algorithm based only on photon beam characteristics, could generate proton DVH-predictions and whether these could correctly identify patients for proton therapy. Material and methodsModelPROT and ModelPHOT comprised 30 head-and-neck cancer proton and photon plans, respectively. Proton and photon knowledge-based-plans (KBPs) were made for ten evaluation-patients. DVH-prediction accuracy was analyzed by comparing predicted-vs-achieved mean OAR doses. KBPs and manual plans were compared using salivary gland and swallowing muscle mean doses. For illustration, patients were selected for protons if predicted ModelPHOT mean dose minus predicted ModelPROT mean dose (ΔPrediction) for combined OARs was ≥6Gy, and benchmarked using achieved KBP doses. ResultsAchieved and predicted ModelPROT/ModelPHOT mean dose R2 was 0.95/0.98. Generally, achieved mean dose for ModelPHOT/ModelPROT KBPs was respectively lower/higher than predicted. Comparing ModelPROT/ModelPHOT KBPs with manual plans, salivary and swallowing mean doses increased/decreased by <2Gy, on average. ΔPrediction≥6Gy correctly selected 4 of 5 patients for protons. ConclusionsKnowledge-based DVH-predictions can provide efficient, patient-specific selection for protons. A proton-specific RapidPlan-solution could improve results.

Individualized Selection of Beam Angles and Treatment Isocenter in Tangential Breast Intensity Modulated Radiation Therapy

Propose a novel method for individualized selection of beam angles and treatment isocenter in tangential breast intensity modulated radiation therapy (IMRT). For each patient, beam and isocenter selection starts with the fully automatic generation of a large database of IMRT plans (up to 847 in this study); each of these plans belongs to a unique combination of isocenter position, lateral beam angle, and medial beam angle. The imposed hard planning constraint on patient maximum dose may result in plans with unacceptable target dose delivery. Such plans are excluded from further analyses. Owing to differences in beam setup, database plans differ in mean doses to organs at risk (OARs). These mean doses are used to construct 2-dimensional graphs, showing relationships between: (1) contralateral breast dose and ipsilateral lung dose; and (2) contralateral breast dose and heart dose (analyzed only for left-sided). The graphs can be used for selection of the isocenter and beam angles with the optimal, patient-specific tradeoffs between the mean OAR doses. For 30 previously treated patients (15 left-sided and 15 right-sided tumors), graphs were generated considering only the clinically applied isocenter with 121 tangential beam angle pairs. For 20 of the 30 patients, 6 alternative isocenters were also investigated. Computation time for automatic generation of 121 IMRT plans took on average 30minutes. The generated graphs demonstrated large variations in tradeoffs between conflicting OAR objectives, depending on beam angles and patient anatomy. For patients with isocenter optimization, 847 IMRT plans were considered. Adding isocenter position optimization next to beam angle optimization had a small impact on the final plan quality. A method is proposed for individualized selection of beam angles in tangential breast IMRT. This may be especially important for patients with cardiac risk factors or an enhanced risk for the development of contralateral breast cancer.

TU‐H‐BRC‐03: Evaluation of Very High‐Energy Electron (VHEE) Beams in Comparison to VMAT and PBS Treatment Plans

Purpose:The aim of this study was to evaluate the performance of very high‐energy electron (VHEE) beams in comparison to clinically delivered treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PBS) technology.Methods:Three clinical cases were selected (prostate, lung, and pediatric CNS). The VHEE plans were calculated in the Monte Carlo EGSnrc code and pencil beam doses were calculated using the DOSxyznrc MC code for 100 and 200 MeV beams. Treatment plans with VHEE, VMAT, and PBS were optimized in a research version of RayStation using an in house build script in order to minimize operator bias between the different techniques.Results:For the prostate cancer case, the PBS plan showed lower mean organ at risk (OAR) doses compared to the other modalities. An exception was the femoral heads, due to the lateral beam arrangements. The VMAT plan showed lower mean doses to the rectum and the bladder compared to the 100 MeV VHEE plan. The lung cancer case showed minor differences between the three modalities. However, the PBS plan showed a lower contralateral lung dose. The pediatric CNS case showed a better conformity and lower spinal cord dose for the 100 MeV VHEE plan. For all cases, the 200 MeV VHEE plans were found to be similar to or better than the 100 MeV VHEE plans.Conclusion:The present study showed that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses can be achieved.Funding: DoD, Award#:W81XWH‐13‐1‐0165, Weston Havens Foundation, Bio‐X (Stanford University), the Office of the Dean of the Medical School, the Office of the Provost (Stanford University), and the Swedish Childhood Cancer Foundation. BL and PM are founders of TibaRay,Inc. BL and PM have received research grants from Varian and RaySearch Laboratory.

Can knowledge-based DVH predictions be used for automated, individualized quality assurance of radiotherapy treatment plans?

BackgroundTreatment plan quality assurance (QA) is important for clinical studies and for institutions aiming to generate near-optimal individualized treatment plans. However, determining how good a given plan is for that particular patient (individualized patient/plan QA, in contrast to running through a checklist of generic QA parameters applied to all patients) is difficult, time consuming and operator-dependent. We therefore evaluated the potential of RapidPlan, a commercial knowledge-based planning solution, to automate this process, by predicting achievable OAR doses for individual patients based on a model library consisting of historical plans with a range of organ-at-risk (OAR) to planning target volume (PTV) geometries and dosimetries.MethodsA 90-plan RapidPlan model, generated using previously created automatic interactively optimized (AIO) plans, was used to predict achievable OAR dose-volume histograms (DVHs) for the parotid glands, submandibular glands, individual swallowing muscles and oral cavities of 20 head and neck cancer (HNC) patients using a volumetric modulated (RapidArc) simultaneous integrated boost technique. Predicted mean OAR doses were compared with mean doses achieved when RapidPlan was used to make a new plan. Differences between the achieved and predicted DVH-lines were analyzed. Finally, RapidPlan predictions were used to evaluate achieved OAR sparing of AIO and manual interactively optimized plans.ResultsFor all OARs, strong linear correlations (R2 = 0.94–0.99) were found between predicted and achieved mean doses. RapidPlan generally overestimated the amount of achievable sparing for OARs with a large degree of OAR-PTV overlap. RapidPlan QA using predicted doses alone identified that for 50 % (10/20) of the manually optimized plans, sparing of the composite salivary glands, oral cavity or composite swallowing muscles could be improved by at least 3 Gy, 5 Gy or 7 Gy, respectively, while this was the case for 20 % (4/20) AIO plans. These predicted gains were validated by replanning the identified patients using RapidPlan.ConclusionsStrong correlations between predicted and achieved mean doses indicate that RapidPlan could accurately predict achievable mean doses. This shows the feasibility of using RapidPlan DVH prediction alone for automated individualized head and neck plan QA. This has applications in individual centers and clinical trials.