Normal Tissue Complication Probability Values Research Articles

Dose-Painting Proton Radiotherapy guided by Functional MRI in Non-Enhancing High-Grade Gliomas

PurposeThis study aimed to demonstrate the feasibility and to evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). Material and methodsThe 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)-(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). ResultsCompared with the IMRT plan, the D2 and D50 of the PRT plan with the same prescription dose increased by 1.27–4.12% and 0.64–2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve > 98% TCP for PRT, and it was 84Gy to achieve > 91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. ConclusionThe functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

Probability of normal tissue complications for hematologic and gastrointestinal toxicity in postoperative whole pelvic radiotherapy for gynecologic malignancies using intensity-modulated proton therapy with robust optimization.

This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.

A Novel Framework for Thermoradiotherapy Treatment Planning

Thermoradiotherapy combines radiation therapy with hyperthermia to increase therapeutic effectiveness. Currently, both modalities are optimized separately and in state-of-the-art research the enhanced therapeutic effect is evaluated using equivalent radiation dose in 2-Gy fractions (EQD2). This study proposes a novel thermoradiotherapy treatment planning framework with voxelwise EQD2 radiation therapy optimizing including thermal radiosensitization and direct thermal cytotoxicity. To demonstrate proof-of-concept of the planning framework, 3 strategies consisting of 20 radiation therapy fractions were planned for 4 prostate cancer cases with substantially different temperature distributions: (1) Conventional radiation therapy plan of 60 Gy combined with 4 hyperthermia sessions (RT60 + HT), (2) standalone uniform dose escalation to 68 Gy without hyperthermia (RT68), and (3) uniform target EQD2 that maximizes the tumor control probability (TCP) accounting for voxelwise thermal effects of 4 hyperthermia sessions without increasing normal tissue doses (RTHT + HT). Assessment included dose, EQD2, TCP, and rectal normal tissue complication probability (NTCP), alongside robustness analyses for TCP and NTCP against parameter uncertainties. The estimated TCP of around 76% for RT60 without hyperthermia was increased to an average of 85.9% (range, 81.3%-90.5%) for RT60 + HT, 92.5% (92.4%-92.5%) for RT68, and 94.4% (91.7%-96.6%) for RTHT + HT. The corresponding averaged rectal NTCPs were 8.7% (7.9%-10.0%), 14.9% (13.8%-17.1%), and 8.4% (7.5%-9.7%), respectively. RT68 and RTHT + HT exhibited slightly enhanced TCP robustness against parameter uncertainties compared with RT60 + HT, and RT68 presented higher and less robust rectal NTCP values compared with the other planning strategies. This study introduces an innovative thermoradiotherapy planning approach, integrating thermal effects into EQD2-based radiation therapy optimization. Results demonstrate an ability to achieve enhanced and uniform target EQD2 and TCP across various temperature distributions without elevating normal tissue EQD2 or NTCP compared with conventional methods. Although promising for improving clinical outcomes, realizable enhancements depend on accurate tumor- and tissue-specific data and precise quantification of hyperthermic effects, which are seamlessly integrable in the planning framework as they emerge.

Dosimetric and radiobiological comparison of IMRT, VMAT, and helical tomotherapy planning techniques in hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases.

To compare treatment planning and dosimetric outcomes for hippocampal sparing whole brain radiotherapy (WBRT) with the simultaneous integrated boost (SIB) in brain metastasis (BM) patients using tumour control probability (TCP) and normal tissue complication probability (NTCP) formalism between IMRT, VMAT, and HT techniques. In this retrospective study, the treatment data of 20 BM patients who typically received whole brain radiation with SIB treatment were used. Prescription doses of 30Gy and 36Gy was delivered in 10 fractions for WBRT and SIB, respectively. Niemierko and LKB models were applied for calculating TCP and NTCP. All the plans were evaluated for the RTOG 0933 protocol criteria and found acceptable. Additionally, the homogeneity of the PTV boost is 0.07 ± 0.01, 0.1 ± 0.04, and 0.08 ± 0.02 for IMRT, VMAT, and HT, respectively (P < 0.05). The percentage of TCP for the PTV boost was 99.99 ± 0.003, 99.98 ± 0.004, and 99.99 ± 0.002 of IMRT, VMAT, and HT, respectively, (P < 0.005). The NTCP value of the lenses was higher with the VMAT plan as compared to IMRT and HT Plans. The hippocampal NTCP values are equal in all three planning proficiencies. The techniques like IMRT, VMAT, and HT can reduce the dose received by hippocampus to the dosimetric threshold during the delivery of WBRT with hippocampal sparing and can simultaneously boost multiple metastases. Overall, the high-quality dose distribution, TCP, and NTCP comparison between all three planning techniques show that the HT technique has better results when compared to the VMAT and IMRT techniques.

Intensity-modulated proton and carbon-ion radiotherapy using a fixed-beam system for locally advanced lung cancer: dosimetric comparison with x-ray radiotherapy and normal tissue complication probability (NTCP) evaluation

Objective. To assess the dosimetric consequences and the normal tissue complication probability (NTCP) for the organs at risk (OARs) in intensity-modulated particle radiotherapy of proton (IMPT) and carbon-ion (IMCT) using a fixed-beam delivery system when compared with intensity-modulated photon radiotherapy (IMRT) for locally advanced small-cell lung cancer. Approach. The plans were all designed under the same total relative biological effectiveness (RBE)-weighted prescription dose, in which the planning target volume (PTV) of the internal gross target volume(IGTV) and the PTV of the clinical target volume was irradiated with 69.3 Gy (RBE) and 63 Gy (RBE), respectively, using a simultaneously integrated boosting (SIB) technique. NTCPs were estimated for heart, lung, esophagus and spinal cord by Lyman–Kutcher–Burman (LKB) and logistic models. Dose escalation was simulated under the desired NTCP values (0.05, 0.10 and 0.50) of the three radiation techniques. Main results. Under the similar target coverage, almost all OARs were significantly better spared (p < 0.05) when using the particle radiotherapy except for D1cc (the dose to 1 cm3 of the volume) of the proximal bronchial tree (p > 0.05). At least 57.6% of mean heart dose, 28.8% of mean lung dose and 19.1% of mean esophageal dose were reduced compared with IMRT. The mean NTCP of radiation-induced pneumonitis (RP) in the ipsilateral lung was 0.39 ± 0.33 (0.39 ± 0.31) in IMPT plans and 0.36 ± 0.32 (0.35 ± 0.30) in IMCT plans compared with 0.66 ± 0.30 (0.64 ± 0.28) in IMRT plans by LKB (logistic) models. The target dose could be escalated to 78.3/76.9 Gy (RBE) in IMPT/IMCT plans compared with 61.7 Gy (RBE) in IMRT plans when 0.50 of NTCP in terms of RP in the ipsilateral lung was applied. Significance. This study presents the potential of better control of the side effects and improvement of local control originating from the dosimetric advantage with the application of IMPT and IMCT with the SIB technique for locally advanced lung cancer, even with limited beam directions.

Comparative dosimetric study of spot-scanning proton therapy versus volumetric-modulated radiation therapy for extrahepatic bile duct cancer

This study aimed to compare the dose distributions and clarify the dosimetric characteristics of spot-scanning proton therapy (SSPT) and photon volumetric modulated arc therapy (VMAT) for extrahepatic bile duct cancer (EBDC). This retrospective study included 10 patients with EBDC treated with real-time image-gated SSPT. Using the simultaneous integrated boost technique, the 2 prescription dose levels for planning target volumes were 72.6 and 44 Gy, delivered in 22 fractions. Plan quality comparisons were conducted by analyzing various parameters, including homogeneity, conformity, dose to organs at risk, and normal tissue complication probability (NTCP) for radiation-induced liver damage (RILD). The target dose distributions using SSPT were almost equivalent to those achieved using photon VMAT. There was a significant reduction in all liver dose parameters, the NTCP value for RILD, and kidney dose (mean, V12 Gy, and V18 Gy) in SSPT than in photon VMAT. No significant differences were observed in the intestinal doses in the high-dose area. Thus, compared with photon VMAT, SSPT for EBDC significantly reduced radiation doses to the liver and kidneys and has shown potential clinical benefits of reduced radiation-induced toxicity.

The dirty and clean dose concept: Towards creating proton therapy treatment plans with a photon-like dose response.

Applying tolerance doses for organs at risk (OAR) from photon therapy introduces uncertainties in proton therapy when assuming a constant relative biological effectiveness (RBE) of 1.1. This work introduces the novel dirty and clean dose concept, which allows for creating treatment plans with a more photon-like dose response for OAR and, thus, less uncertainties when applying photon-based tolerance doses. The concept divides the 1.1-weighted dose distribution into two parts: the clean and the dirty dose. The clean and dirty dose are deposited by protons with a linear energy transfer (LET) below and above a set LET threshold, respectively. For the former, a photon-like dose response is assumed, while for the latter, the RBE might exceed 1.1. To reduce the dirty dose in OAR, a MaxDirtyDose objective was added in treatment plan optimization. It requires setting two parameters: LET threshold and max dirty dose level. A simple geometry consisting of one target volume and one OAR in water was used to study the reduction in dirty dose in the OAR depending on the choice of the two MaxDirtyDose objective parameters during plan optimization. The best performing parameter combinations were used to create multiple dirty dose optimized (DDopt) treatment plans for two cranial patient cases. For each DDopt plan, 1.1-weighted dose, variable RBE-weighted dose using the Wedenberg RBE model and dose-average LETd distributions as well as resulting normal tissue complication probability (NTCP) values were calculated and compared to the reference plan (RefPlan) without MaxDirtyDose objectives. In the water phantom studies, LET thresholds between 1.5 and 2.5keV/µm yielded the best plans and were subsequently used. For the patient cases, nearly all DDopt plans led to a reduced Wedenberg dose in critical OAR. This reduction resulted from an LET reduction and translated into an NTCP reduction of up to 19 percentage points compared to the RefPlan. The 1.1-weighted dose in the OARs was slightly increased (patient 1: 0.45Gy(RBE), patient 2: 0.08Gy(RBE)), but never exceeded clinical tolerance doses. Additionally, slightly increased 1.1-weighted dose in healthy brain tissue was observed (patient 1: 0.81Gy(RBE), patient 2: 0.53Gy(RBE)). The variation of NTCP values due to variation of α/β from 2 to 3Gy was much smaller for DDopt (2 percentage points (pp)) than for RefPlans (5 pp). The novel dirty and clean dose concept allows for creating biologically more robust proton treatment plans with a more photon-like dose response. The reduced uncertainties in RBE can, therefore, mitigate uncertainties introduced by using photon-based tolerance doses for OAR.

Comparing Predicted Toxicities between Hypofractionated Proton and Photon Radiotherapy of Liver Cancer Patients with Different Adaptive Schemes.

With the availability of MRI linacs, online adaptive intensity modulated radiotherapy (IMRT) has become a treatment option for liver cancer patients, often combined with hypofractionation. Intensity modulated proton therapy (IMPT) has the potential to reduce the dose to healthy tissue, but it is particularly sensitive to changes in the beam path and might therefore benefit from online adaptation. This study compares the normal tissue complication probabilities (NTCPs) for liver and duodenal toxicity for adaptive and non-adaptive IMRT and IMPT treatments of liver cancer patients. Adaptive and non-adaptive IMRT and IMPT plans were optimized to 50 Gy (RBE = 1.1 for IMPT) in five fractions for 10 liver cancer patients, using the original MRI linac images and physician-drawn structures. Three liver NTCP models were used to predict radiation-induced liver disease, an increase in albumin-bilirubin level, and a Child-Pugh score increase of more than 2. Additionally, three duodenal NTCP models were used to predict gastric bleeding, gastrointestinal (GI) toxicity with grades >3, and duodenal toxicity grades 2-4. NTCPs were calculated for adaptive and non-adaptive IMRT and IMPT treatments. In general, IMRT showed higher NTCP values than IMPT and the differences were often significant. However, the differences between adaptive and non-adaptive treatment schemes were not significant, indicating that the NTCP benefit of adaptive treatment regimens is expected to be smaller than the expected difference between IMRT and IMPT.

Relationship between the Patients’ Setup Errors with Dosimetric and Radiobiologic Parameters in Whole Breast Radiotherapy

Purpose: This study aimed to investigate the effect of the patients’ setup errors on dosimetric and radiobiologic parameters for left-sided Whole-Breast Irradiation (WBI) in three different radiotherapy techniques, including Intensity-Modulated Radiation Therapy (IMRT), Field-In-Field (FIF), and Conventional Wedge (CW).&#x0D; Materials and Methods: Computed Tomography (CT) images of 10 female patients with early-stage left-sided breast cancer were used to simulate different radiotherapy techniques (IMRT, FIF, and CW). The dosimetric parameters; Conformity Index (CI), Homogeneity Index (HI), the dose received by at least 95% (D95%) of Planning Tumor Volume (PTV), the volume of lung and heart that respectively received at least 20% (V20%) and 40% (V40%) of the prescribed dose, as well as, the radiobiologic parameters, including Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) were assessed for setup errors in patients. The setup errors were assessed by shifting the isocenters and gantry angles of the treatment plans.&#x0D; Results: The D95% of the PTV for an isocenter misplacement plan in the posterior direction decreased by 66.99 (IMRT), 71.86 (CW), and 68.25% (FIF). The TCP of the PTV was reduced by 26.66, 39.16, and 36.97% for IMRT, CW, and FIF techniques, respectively. Increasing gantry angle by a ±10 degree caused a 43%, 41%, and 41% decrease in the D95% of IMRT, FIF, and CW techniques, respectively. The TCP values decreased about 18% in all three techniques with a ±10 degree gantry angle shift; however, the NTCP values of the heart and lungs increased for all three methods. The CI and HI values had significantly more changes with increasing setup errors in the IMRT than in the two techniques.&#x0D; Conclusion: The radiobiologic parameters in IMRT were less sensitive to setup errors compared to FIF and CW techniques. The radiobiological parameters can help estimate the setup errors along with physical parameters during breast radiotherapy.

Evaluating the effect of setup uncertainty reduction and adaptation to geometric changes on normal tissue complication probability using online adaptive head and neck intensity modulated proton therapy

Objective. To evaluate the impact of setup uncertainty reduction (SUR) and adaptation to geometrical changes (AGC) on normal tissue complication probability (NTCP) when using online adaptive head and neck intensity modulated proton therapy (IMPT). Approach. A cohort of ten retrospective head and neck cancer patients with daily scatter corrected cone-beam CT (CBCT) was studied. For each patient, two IMPT treatment plans were created: one with a 3 mm setup uncertainty robustness setting and one with no explicit setup robustness. Both plans were recalculated on the daily CBCT considering three scenarios: the robust plan without adaptation, the non-robust plan without adaptation and the non-robust plan with daily online adaptation. Online-adaptation was simulated using an in-house developed workflow based on GPU-accelerated Monte Carlo dose calculation and partial spot-intensity re-optimization. Dose distributions associated with each scenario were accumulated on the planning CT, where NTCP models for six toxicities were applied. NTCP values from each scenario were intercompared to quantify the reduction in toxicity risk induced by SUR alone, AGC alone and SUR and AGC combined. Finally, a decision tree was implemented to assess the clinical significance of the toxicity reduction associated with each mechanism. Main results. For most patients, clinically meaningful NTCP reductions were only achieved when SUR and AGC were performed together. In these conditions, total reductions in NTCP of up to 30.48 pp were obtained, with noticeable NTCP reductions for aspiration, dysphagia and xerostomia (mean reductions of 8.25, 5.42 and 5.12 pp respectively). While SUR had a generally larger impact than AGC on NTCP reductions, SUR alone did not induce clinically meaningful toxicity reductions in any patient, compared to only one for AGC alone. Significance Online adaptive head and neck proton therapy can only yield clinically significant reductions in the risk of long-term side effects when combining the benefits of SUR and AGC.

Multiple Brain Metastases Radiosurgery with CyberKnife Device: Dosimetric Comparison between Fixed/Iris and Multileaf Collimator Plans.

In our institution, stereotactic radiosurgery of multiple brain metastases is performed with the CyberKnife® (CK) device, using fixed/Iris collimators. In this study, nineteen fixed/Iris plans were recalculated with the multileaf collimator (MLC), to assess if it is possible to produce plans with comparable dosimetric overall quality. For consistent comparisons, MLC plans were re-optimized and re-normalized in order to achieve the same minimum dose for the total planning target volume (PTVtot). Conformation number (CN), homogeneity index (HI) and dose gradient index (DGI) metrics were evaluated. The dose to the brain was evaluated as the volume receiving 12 Gy (V12) and as the integral dose (ID). The normal tissue complication probability (NTCP) for brain radionecrosis was calculated as a function of V12. The reoptimized plans were reviewed by the radiation oncologist and were found clinically acceptable according to the The American Association of Physicists in Medicine (AAPM) Task Group-101 protocol. However, fixed/Iris plans provided significantly higher CN (+8.6%), HI (+2.2%), and DGI (+44.0%) values, and significantly lower ID values (-35.9%). For PTVtot less than the median value of 2.58cc, fixed/Iris plans provided significantly lower NTCP values. On the other side, MLC plans provided significantly lower treatment times (-18.4%), number of monitor units (-33.3%), beams (-46.0%) and nodes (-21.3%). CK-MLC plans for the stereotactic treatment of brain multi metastases could provide an important advantage in terms of treatment duration. However, to contain the increased risk for brain radionecrosis, it could be useful to calculate MLC plans only for patients with large PTVtot.

Comparison of intensity-modulated proton therapy (IMPT) versus intensity-modulated radiation therapy (IMRT) for the treatment of head and neck cancer based on radiobiological modelling

Abstract Aim: The aim of our study is to retrospectively report the radiobiological aspects for intensity-modulated proton therapy (IMPT) against intensity-modulated radiation therapy (IMRT) for patients with head and neck cancer treated at our institution. A secondary goal is to reinforce current model-based approaches to head and neck cancer patient selection for IMPT. Materials and Methods: Eighteen patients were evaluated with prescription doses ranging from 50 to 70 Gy delivered in 2 Gy per fraction. The dose volume histograms (DVH) were used to calculate equivalent uniform dose (EUD), tumour control probability (TCP) and normal tissue complication probability (NTCP) for biophysical comparison using mechanistic mathematical dose response models. Absolute values of TCP and NTCP were then compared between IMPT and IMRT. Results: The dose models demonstrate a minimal radiobiological advantage for IMPT compared to IMRT in treating head and neck cancers. Absolute values of TCP were slightly higher, while absolute values of NTCP were slightly lower for IMPT versus IMRT. Conclusions: Further studies are needed to determine if the radiobiological advantage indeed translates to a therapeutic advantage for patients.

A Dosimetric and Radiobiological Comparison of Intensity Modulated Radiotherapy, Volumetric Modulated Arc Therapy and Helical Tomotherapy Planning Techniques in Synchronous Bilateral Breast Cancer

The present investigation intends to identify the optimal radiotherapy treatment plan for synchronous bilateral breast cancer (SBBC) using dosimetric and radiobiological indexes for three techniques, namely, helical tomotherapy (HT), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT). Twenty SBBC treated female patients treatment planning data (average age of 52.5 years) were used as the sample for the present study. Three different plans were created using 50 Gy in a 25 fraction dose regime. Poisson, Niemierko, and LKB models were applied for calculating normal tissue complication probability (NTCP) and tumour control probability (TCP). The target average dose comparison between IMRT with HT and VMAT with HT was highly substantial (P=0.001). The percentage of TCP for IMRT, VMAT, and HT in the Poisson model were 93.70±0.28, 94.68±0.30, and 94.34±0.57, respectively (p<0.05). The dose maximum was lower for the whole lung in the HT plan, with an average dose of 49.31Gy±3.9 (p<0.009). The NTCP values of both Niemierko and LKB models were lower for the heart, lungs, and liver for the IMRT plan. The sparing of organs at risk was higher in the HT plan dosimetrically, and the TCP was higher in the three techniques. The comparison between the three techniques shows that the IMRT and HT techniques could be considered for treating SBBC.

Leveraging deep learning-based segmentation and contours-driven deformable registration for dose accumulation in abdominal structures

Discrepancies between planned and delivered dose to GI structures during radiation therapy (RT) of liver cancer may hamper the prediction of treatment outcomes. The purpose of this study is to develop a streamlined workflow for dose accumulation in a treatment planning system (TPS) during liver image-guided RT and to assess its accuracy when using different deformable image registration (DIR) algorithms. Fifty-six patients with primary and metastatic liver cancer treated with external beam radiotherapy guided by daily CT-on-rails (CTOR) were retrospectively analyzed. The liver, stomach and duodenum contours were auto-segmented on all planning CTs and daily CTORs using deep-learning methods. Dose accumulation was performed for each patient using scripting functionalities of the TPS and considering three available DIR algorithms based on: (i) image intensities only; (ii) intensities + contours; (iii) a biomechanical model (contours only). Planned and accumulated doses were converted to equivalent dose in 2Gy (EQD2) and normal tissue complication probabilities (NTCP) were calculated for the stomach and duodenum. Dosimetric indexes for the normal liver, GTV, stomach and duodenum and the NTCP values were exported from the TPS for analysis of the discrepancies between planned and the different accumulated doses. Deep learning segmentation of the stomach and duodenum enabled considerable acceleration of the dose accumulation process for the 56 patients. Differences between accumulated and planned doses were analyzed considering the 3 DIR methods. For the normal liver, stomach and duodenum, the distribution of the 56 differences in maximum doses (D2%) presented a significantly higher variance when a contour-driven DIR method was used instead of the intensity only-based method. Comparing the two contour-driven DIR methods, differences in accumulated minimum doses (D98%) in the GTV were >2Gy for 15 (27%) of the patients. Considering accumulated dose instead of planned dose in standard NTCP models of the duodenum demonstrated a high sensitivity of the duodenum toxicity risk to these dose discrepancies, whereas smaller variations were observed for the stomach. This study demonstrated a successful implementation of an automatic workflow for dose accumulation during liver cancer RT in a commercial TPS. The use of contour-driven DIR methods led to larger discrepancies between planned and accumulated doses in comparison to using an intensity only based DIR method, suggesting a better capability of these approaches in estimating complex deformations of the GI organs.

Dosimetric comparison between VMAT plans using the fast-rotating O-ring linac with dual-layer stacked MLC and helical tomotherapy for nasopharyngeal carcinoma

BackgroundTo compare the dosimetric profiles of volumetric modulated arc therapy (VMAT) plans using the fast-rotating O-ring linac (the Halcyon system) based on a dual-layer stacked multi-leaf collimator and helical tomotherapy (HT) for nasopharyngeal cancer (NPCa).MethodsFor 30 NPCa patients, three sets of RT plans were generated, under the same policy of contouring and dose constraints: HT plan; Halcyon VMAT plan with two arcs (HL2arc); and Halcyon VMAT plan with four arcs (HL4arc), respectively. The intended dose schedule was to deliver 67.2 Gy to the planning gross target volume (P-GTV) and 56.0 Gy to the planning clinical target volume (P-CTV) in 28 fractions using the simultaneously integrated boost concept. Target volumes and organ at risks dose metrics were evaluated for all plans. Normal tissue complication probabilities (NTCP) for esophagus, parotid glands, spinal cord, and brain stem were compared.ResultsThe HT plan achieved the best dose homogeneity index for both P_GTV and P_CTV, followed by the HL4arc and L2arc plans. No significant difference in the dose conformity index (CI) for P_GTV was observed between the HT plan (0.80) and either the HL2arc plan (0.79) or the HL4arc plan (0.83). The HL4arc plan showed the best CI for P_CTV (0.88), followed by the HL2arc plan (0.83) and the HT plan (0.80). The HL4arc plan (median, interquartile rage (Q1, Q3): 25.36 (22.22, 26.89) Gy) showed the lowest Dmean in the parotid glands, followed by the HT (25.88 (23.87, 27.87) Gy) and HL2arc plans (28.00 (23.24, 33.99) Gy). In the oral cavity (OC) dose comparison, the HT (22.03 (19.79, 24.85) Gy) plan showed the lowest Dmean compared to the HL2arc (23.96 (20.84, 28.02) Gy) and HL4arc (24.14 (20.17, 27.53) Gy) plans. Intermediate and low dose regions (40–65% of the prescribed dose) were well fit to the target volume in HL4arc, compared to the HT and HL2arc plans. All plans met the dose constraints for the other OARs with sufficient dose margins. The between-group differences in the median NTCP values for the parotid glands and OC were < 3.47% and < 1.7% points, respectively.ConclusionsThe dosimetric profiles of Halcyon VMAT plans were comparable to that of HT, and HL4arc showed better dosimetric profiles than HL2arc for NPCa.

Evaluation of the clinical impact of the differences between planned and delivered dose in prostate cancer radiotherapy based on CT-on-rails IGRT and patient-reported outcome scores.

To estimate the clinical impact of differences between delivered and planned dose using dose metrics and normal tissue complication probability (NTCP) modeling. Forty-six consecutive patients with prostate adenocarcinoma between 2010 and 2015 treated with intensity-modulated radiation therapy (IMRT) and who had undergone computed tomography on rails imaging were included. Delivered doses to bladder and rectum were estimated using a contour-based deformable image registration method. The bladder and rectum NTCP were calculated using dose-response parameters applied to planned and delivered dose distributions. Seven urinary and gastrointestinal symptoms were prospectively collected using the validated prostate cancer symptom indices patient reported outcome (PRO) at pre-treatment, weekly treatment, and post-treatment follow-up visits. Correlations between planned and delivered doses against PRO were evaluated in this study. Planned mean doses to bladder and rectum were 44.9 ± 13.6 Gy and 42.8 ± 7.3 Gy, while delivered doses were 46.1 ± 13.4 Gy and 41.3 ± 8.7 Gy, respectively. D10cc for rectum was 64.1 ± 7.6 Gy for planned and 60.1 ± 9.3 Gy for delivered doses. NTCP values of treatment plan were 22.3% ± 8.4% and 12.6% ± 5.9%, while those for delivered doses were 23.2% ± 8.4% and 9.9% ± 8.3% for bladder and rectum, respectively. Seven of 25 patients with follow-up data showed urinary complications (28%) and three had rectal complications (12%). Correlations of NTCP values of planned and delivered doses with PRO follow-up data were random for bladder and moderate for rectum (0.68 and 0.67, respectively). Sensitivity of bladder to clinical variations of dose accumulation indicates that an automated solution based on a DIR that considers inter-fractional organ deformation could recommend intervention. This is intended to achieve additional rectum sparing in cases that indicate higher than expected dose accumulation early during patient treatment in order to prevent acute severity of bowel symptoms.

Parameters of the Lyman Model for Calculation of Normal-Tissue Complication Probability: A Systematic Literature Review

The Lyman model is one of the most used radiobiological models for calculation of normal-tissue complication probability (NTCP). Since its introduction in 1985, many authors have published parameter values for the model based on clinical data of different radiotherapeutic situations. This study attempted to collect the entirety of radiobiological parameter sets published to date and provide an overview of the data basis for different variations of the model. Furthermore, it sought to compare the parameter values and calculated NTCPs for selected endpoints with sufficient data available. A systematic literature analysis was performed, searching for publications that provided parameters for the different variations of the Lyman model in the Medline database using PubMed. Parameter sets were grouped into 13 toxicity-related endpoint groups. For 3 selected endpoint groups (≤25% reduction of saliva 12 months after irradiation of the parotid, symptomatic pneumonitis after irradiation of the lung, and bleeding of grade 2 or less after irradiation of the rectum), parameter values were compared and differences in calculated NTCP values were analyzed. A total of 509 parameter sets from 130 publications were identified. Considerable heterogeneities were detected regarding the number of parameters available for different radio-oncological situations. Furthermore, for the 3 selected endpoints, large differences in published parameter values were found. These translated into great variations of calculated NTCPs, with maximum ranges of 35.2% to 93.4% for the saliva endpoint, of 39.4% to 90.4% for the pneumonitis endpoint, and of 5.4% to 99.3% for the rectal bleeding endpoint. The detected heterogeneity of the data as well as the large variations of published radiobiological parameters underline the necessity for careful interpretation when using such parameters for NTCP calculations. Appropriate selection of parameters and validation of values are essential when using the Lyman model.

Analysis of deep inspiration breath-hold technique to improve dosimetric and clinical advantages in postoperative intensity-modulated radiation therapy for thymomas.

BackgroundRadiation therapy is one of the essential treatment modalities for invasive thymomas. Clinically, respiratory motion poses a challenge for the radiotherapy of thoracic tumors. One method to address this issue is to train patients to hold their breath at the end of deep inspiration. The purpose of this retrospective cohort study was to investigate the dosimetric and clinical advantages of the deep inspiration breath-hold (DIBH) technique in postoperative intensity-modulated radiation therapy (IMRT) for thymomas.MethodsThymoma patients undergoing postoperative IMRT were included. Each patient underwent two computed tomography (CT) scans, one under free breath (FB) and the other under DIBH. Dosimetric parameters of organs at risk (OARs) were evaluated in three series plans. Dose analysis and volume comparisons were conducted during FB-3 mm (FB with 3 mm internal target volume margin), FB-10 mm (FB with 10 mm internal target volume margin), and DIBH and compared using a paired sample Student’s t-test. Normal tissue complication probabilities (NTCP) for lungs and heart were calculated and compared.ResultsThe total lung volume significantly increased by 31% (4,216±198 vs. 2,884±166 mL) and the heart volume reduced by 12% (552±25 vs. 636±35 mL) between DIBH acquisitions compared to FB. A significant improvement was observed in all the dosimetric parameters (Dmean, V20, V5) of the lung on DIBH compared to FB-3 mm (54%±2.85% vs. 47%±2.90%, P<0.001; 15%±1.37% vs. 12%±1.32%, P=0.004; and 10.28±0.58 vs. 8.76±0.57 Gy, P<0.001, respectively), as well as in the Dmax and D2% of the esophagus and spine. The lung volume increment was related to a reduction in the mean dose of lungs, with a correlation coefficient of r=0.27, P=0.03. The NTCP values for pneumonitis significantly reduced with DIBH compared to the FB state (0.6% vs. 1.1%, P<0.001).ConclusionsThe radiation dose to the OARs can be significantly reduced by using the DIBH technique in postoperative IMRT for thymomas. The increased volume of lungs using DIBH acquisitions can significantly reduce the incidence of pneumonitis.

Comparison of Estimated Late Toxicities between IMPT and IMRT Based on Multivariable NTCP Models for High-Risk Prostate Cancers Treated with Pelvic Nodal Radiation.

PurposeTo compare the late gastrointestinal (GI) and genitourinary toxicities (GU) estimated using multivariable normal tissue complication probability (NTCP) models, between pencil-beam scanning proton beam therapy (PBT) and helical tomotherapy (HT) in patients of high-risk prostate cancers requiring pelvic nodal irradiation (PNI) using moderately hypofractionated regimen.Materials and MethodsTwelve consecutive patients treated with PBT at our center were replanned with HT using the same planning goals. Six late GI and GU toxicity domains (stool frequency, rectal bleeding, fecal incontinence, dysuria, urinary incontinence, and hematuria) were estimated based on the published multivariable NTCP models. The ΔNTCP (difference in absolute NTCP between HT and PBT plans) for each of the toxicity domains was calculated. A one-sample Kolmogorov-Smirnov test was used to analyze distribution of data, and either a paired t test or a Wilcoxon matched-pair signed rank test was used to test statistical significance.ResultsProton beam therapy and HT plans achieved adequate target coverage. Proton beam therapy plans led to significantly better sparing of bladder, rectum, and bowel bag especially in the intermediate range of 15 to 40 Gy, whereas doses to penile bulb and femoral heads were higher with PBT plans. The average ΔNTCP for grade (G)2 rectal bleeding, fecal incontinence, stool frequency, dysuria, urinary incontinence, and G1 hematuria was 12.17%, 1.67%, 2%, 5.83%, 2.42%, and 3.91%, respectively, favoring PBT plans. The average cumulative ΔNTCP for GI and GU toxicities (ΣΔNTCP) was 16.58% and 11.41%, respectively, favoring PBT. Using a model-based selection threshold of any G2 ΔNTCP >10%, 67% (8 patients) would be eligible for PBT.ConclusionProton beam therapy plans led to superior sparing of organs at risk compared with HT, which translated to lower NTCP for late moderate GI and GU toxicities in patients of prostate cancer treated with PNI. For two-thirds of our patients, the difference in estimated absolute NTCP values between PBT and HT crossed the accepted threshold for minimal clinically important difference.

A study on predicting cases that would benefit from proton beam therapy in primary liver tumors of less than or equal to 5 cm based on the estimated incidence of hepatic toxicity

BackgroundFor small primary liver tumors, favorable outcomes have been reported with both of proton beam therapy (PBT) and X-ray therapy (XRT). However, no clear criteria have been proposed in the cases for which and when of PBT or XRT has to be used. The aim of this study is to investigate cases that would benefit from PBT based on the predicted rate of hepatic toxicity. Materials and methodsEligible patients were those who underwent PBT for primary liver tumors with a maximum diameter of ≤ 5 cm and Child-Pugh grade A (n = 40). To compare the PBT-plan, the treatment plan using volumetric modulated arc therapy was generated as the XRT-plan. The rate of predicted hepatic toxicity was estimated using five normal tissue complication probability (NTCP) models with three different endpoints. The differences in NTCP values (ΔNTCP) were calculated to determine the relative advantage of PBT. Factors predicting benefits of PBT were analyzed by logistic regression analysis. ResultsFrom the dose-volume histogram comparisons, an advantage of PBT was found in sparing of the normal liver receiving low doses. The factors predicting the benefit of PBT differed depending on the selected NTCP model. From the five models, the total tumor diameter (sum of the target tumors), location (hepatic hilum vs other), and number of tumors (1 vs 2) were significant factors. ConclusionsFrom the radiation-related hepatic toxicity, factors were identified to predict benefits of PBT in primary liver tumors with Child-Pugh grade A, with the maximum tumor diameter of ≤ 5 cm.