EVALUATION OF AN END-TO-END RADIOTHERAPY TREATMENT PLANNING PIPELINE FOR PROSTATE CANCER

Radiation treatment planning is a crucial and time-intensive process in radiation therapy. This planning involves carefully designing a treatment regimen tailored to a patient’s specific condition, including the type, location, and size of the tumor with reference to surrounding healthy tissues. For prostate cancer, this tumor may be either local, locally advanced with extracapsular involvement, or extend into the pelvic lymph node chain. Automating essential parts of this process would allow for the rapid development of effective treatment plans and better plan optimization to enhance tumor control for better outcomes. The first objective of this work, to automate the treatment planning process, was the automatic segmentation of critical structures. Delineation of both target and normal tissue structures was necessary to establish the foundation for identifying where radiation must be delivered and what should be spared from excess radiation. Deep learning segmentation models were developed from retrospective CT simulation imaging data and clinical contours to delineate intact, postoperative, and nodal treatment structures for prostate cancer to accomplish this objective. Quality contours were extracted per established contouring guidelines in the literature. Model refinement on a holdout fine-tune dataset was used to verify model contours before quantitative and qualitative evaluation on the holdout test set. Predicted contours resulted in contours comparable in quantitative Dice-Similarity-Coefficient (DSC) and 95% Hausdorff Distance (HD95) to proposed models in literature and clinically usable contours with no more than minor edits upon physician review. The second objective was the automation of Volumetric Modulated Arc Therapy (VMAT) planning for a breadth of prostate treatment scenarios. Development of VMAT plans for intact, postoperative, and nodal involvement treatment cases was necessary for the sequence in daily treatment delivery and the prospective distribution of radiation dose to target and normal tissues. To accomplish this objective, knowledge-based planning models were separately developed to estimate patient-specific DVHs to guide plan optimization for radiation delivery. These two models were then used in this work for end-to-end testing of cases with and without lymph node involvement, including determining if the prostate target is intact or postoperative with or without treatment devices such as hydrogel spacers and rectal balloons. A sequence of iterative optimization runs was created to ensure hotspot reduction and target conformality. The findings demonstrated that plans developed from automatically generated contours were clinically usable with minor edits for intact and postoperative treatments without lymph node involvement. For treatments with lymph node involvement, dose constraints were met for a select set of cases without excessive rectum curvature or excessive bladder descension into the postoperative treatment bed. When comparing auto-segmented to clinical contours, clinical contours experienced similar pass rates as those achieved by auto-segmented contours

Intensity modulated proton arc therapy via geometry-based energy selection for ependymoma

We developed a novel method of creating intensity modulated proton arc therapy (IMPAT) plans that uses computing resources efficiently and may offer a dosimetric benefit for patients with ependymoma or similar tumor geometries. Our IMPAT planning method consists of a geometry-based energy selection step with major scanning spot contributions as inputs computed using ray-tracing and single-Gaussian approximation of lateral spot profiles. Based on the geometric relation of scanning spots and dose voxels, our energy selection module selects a minimum set of energy layers at each gantry angle such that each target voxel is covered by sufficient scanning spots as specified by the planner, with dose contributions above the specified threshold. Finally, IMPAT plans are generated by robustly optimizing scanning spots of the selected energy layers using a commercial proton treatment planning system. The IMPAT plan quality was assessed for four ependymoma patients. Reference three-field IMPT plans were created with similar planning objective functions and compared with the IMPAT plans. In all plans, the prescribed dose covered 95% of the clinical target volume (CTV) while maintaining similar maximum doses for the brainstem. While IMPAT and IMPT achieved comparable plan robustness, the IMPAT plans achieved better homogeneity and conformity than the IMPT plans. The IMPAT plans also exhibited higher relative biological effectiveness (RBE) enhancement than did the corresponding reference IMPT plans for the CTV in all four patients and brainstem in three of them. The proposed method demonstrated potential as an efficient technique for IMPAT planning and may offer a dosimetric benefit for patients with ependymoma or tumors in close proximity to critical organs. IMPAT plans created using this method had elevated RBE enhancement associated with increased linear energy transfer.Comment: 24 pages with 8 figures and 2 table

Biological Dose Comparison between a Fixed RBE and a variable RBE in SFO and MFO IMPT with Various Multi-Beams for Brain Cancer

IMPT plans with various multi-angle beams were planned by the Varian Ec- lipse treatment planning system for one case of brain cancer. Dose distribu- tions for each plan, along with the associated linear energy transfer distribu- tions, were recomputed using an in-house fast Monte Carlo dose calculator with a FRBE of 1.1 or with a previously published VRBE model. We then compared dosimetric parameters obtained by the VRBE with those obtained by the FRBE. Biological doses obtained by the VRBE for the clinical target volume in all plans were 1% - 2% larger than those obtained by the FRBE. The minimum dose obtained by the VRBE for the right optic nerve in the MFO IMPT with 4 fields was 70% larger than that obtained by the FRBE, but the difference was only 18.1 cGy (RBE). The difference in maximum dose for the right optic nerve in the MFO IMPT with 5 fields was less than 10.4%, but the difference was 131.8 cGy (RBE). The mean difference in maximum dose was less than 2% for all other organs at risk. We found that biological dose with the FRBE had any dose errors in IMPT with various multi-angle beams

IMPTにおけるvariable RBE計算による線量評価

目的：高速モンテカルロ法であるfast dose calculator（FDC）により求められた線量とLETを用いてRBEを計算し、最先端陽子線治療であるIMPTに対して線量評価を行う。方法：腫瘍周辺をリスク臓器が覆うような脳腫瘍症例を選択した。その症例に対して、Eclipse治療計画装置を用いて、IMPTを計画した。ここで、その治療計画に対して、Yepseらが開発したFDCにより計算を実施し、線量やLETを求めた。FDCは、水に対して事前にGEANTシミュレーションを行っておいて、その結果を使って、任意の物質に対しては、長さや散乱角をスケーリングすることで、線量計算を行う方法で、計算時間は患者当たり５分と短い。そして、FDCにより計算された線量やLETに加え、組織パラメータを関数とするWilkensらによって開発されたRBE計算モデルを用いて線量計算を実施した。なお、各部位毎のRBEを計算するために、Freseらによって与えられた生物パラメータを用いた。このようにして計算されたCTVやリスク臓器における線量について、従来のRBE=1.1としたfixed RBEによる線量計算結果と比較した。結果：GTVやCTVにおいてvariable RBEは、fix RBEに比べて、最小線量と最大線量に対する線量は、約２％程度高かった。一方、脳幹の最小線量では、128%の線量差が観測されたが、最大線量では、２％であった。また、右視神経では、最小線量の差は４０％で、最大線量の差は１９％であった。結論：IMPT治療計画に対して、FDCにより線量計算を実施し、Wilkensらによって開発されたRBE計算モデルを用いてRBE計算を実行した。RBE計算の違いによるGTVやCTVにおける線量差は、２％程度であったが、部位によっては、最小線量の差が大きく出ることがわかった

Biological dose calculation using variable RBE in Single- and Multi-field Optimization IMPT plans for 3 Brain Tumor patients

Purpose: The purpose of this study was to evaluate biological dose in single-field optimization (SFO) and multi-field optimization (MFO) intensity-modulated proton therapy (IMPT) plans for brain tumor patients that used a fixed relative biological effectiveness (FRBE) and those that used a variable RBE (VRBE). Materials and methods: SFO and MFO IMPT plans were planned by the Varian Eclipse treatment planning system for three brain tumor patients. Dose and linear energy transfer (LET) distributions for each plan were recomputed using an in-house fast Monte Carlo dose calculator system, and then biological dose distributions were calculated with a FRBE of 1.1 or with a previously published VRBE model. We then compared biological dose distributions obtained by the VRBE with those obtained by the FRBE. Results: Doses obtained by the VRBE for the gross tumor volume and clinical target volume in all plans were 1%-2% larger than those obtained by the FRBE. The minimum dose obtained by the VRBE for the brainstem in the SFO IMPT of one patient was 140% larger than that obtained by the FRBE, but the difference was only 5.3 cGy (RBE). The difference in maximum dose for the optic chiasm in the MFO IMPT of another patient was less than 3.2%, but the dose difference was 149.2 cGy (RBE). We also found that no major differences were seen between the biological dose differences in the SFO IMPT plans and those in the MFO IMPT plans. Conclusion: We could observe biological dose differences between the FRBE and the VRBE in the SFO and the MFO IMPT plans for brain tumor patients

Towards Effective and Efficient Patient-Specific Quality Assurance for Spot Scanning Proton Therapy

An intensity-modulated proton therapy (IMPT) patient-specific quality assurance (PSQA) program based on measurement alone can be very time consuming due to the highly modulated dose distributions of IMPT fields. Incorporating independent dose calculation and treatment log file analysis could reduce the time required for measurements. In this article, we summarize our effort to develop an efficient and effective PSQA program that consists of three components: measurements, independent dose calculation, and analysis of patient-specific treatment delivery log files. Measurements included two-dimensional (2D) measurements using an ionization chamber array detector for each field delivered at the planned gantry angles with the electronic medical record (EMR) system in the QA mode and the accelerator control system (ACS) in the treatment mode, and additional measurements at depths for each field with the ACS in physics mode and without the EMR system. Dose distributions for each field in a water phantom were calculated independently using a recently developed in-house pencil beam algorithm and compared with those obtained using the treatment planning system (TPS). The treatment log file for each field was analyzed in terms of deviations in delivered spot positions from their planned positions using various statistical methods. Using this improved PSQA program, we were able to verify the integrity of the data transfer from the TPS to the EMR to the ACS, the dose calculation of the TPS, and the treatment delivery, including the dose delivered and spot positions. On the basis of this experience, we estimate that the in-room measurement time required for each complex IMPT case (e.g., a patient receiving bilateral IMPT for head and neck cancer) is less than 1 h using the improved PSQA program. Our experience demonstrates that it is possible to develop an efficient and effective PSQA program for IMPT with the equipment and resources available in the clinic

Synchrotron-Based Pencil Beam Scanning Nozzle with an Integrated Mini-Ridge Filter: A Dosimetric Study to Optimize Treatment Delivery

A mini-ridge filter is often used to widen the Bragg peak in the longitudinal direction at low energies but not high energies. To facilitate the clinical use of a mini-ridge filter, we performed a planning study for the feasibility of a mini-ridge filter as an integral part of the synchrotron nozzle (IMRF). Dose models with and without IMRF were commissioned in a commercial Treatment planning system (TPS). Dosimetric characteristics in a homogenous water phantom were compared between plans with and without IMRF for a fixed spread-out Bragg peak width of 4 cm with distal ranges varying from 8 to 30 g/cm2. Six clinical cases were then used to compare the plan quality between plans. The delivery efficiency was also compared between plans in both the phantom and the clinical cases. The Bragg peak width was increased by 0.18 cm at the lowest energy and by only about 0.04 cm at the highest energy. The IMRF increased the spot size (σ) by up to 0.1 cm at the lowest energy and by only 0.02 cm at the highest energy. For the phantom, the IMRF negligibly affected dose at high energies but increased the lateral penumbra by up to 0.12 cm and the distal penumbra by up to 0.06 cm at low energies. For the clinical cases, the IMRF slightly increased dose to the organs at risk. However, the beam delivery time was reduced from 18.5% to 47.1% for the lung, brain, scalp, and head and neck cases, and dose uniformities of target were improved up to 2.9% for these cases owing to the reduced minimum monitor unit effect. In conclusion, integrating a mini-ridge filter into a synchrotron nozzle is feasible for improving treatment efficiency without significantly sacrificing the plan quality

Exploration of the potential of liquid scintillators for real-time 3D dosimetry of intensity modulated proton beams

In this study, the authors investigated the feasibility of using a 3D liquid scintillator (LS) detector system for the verification and characterization of proton beams in real time for intensity and energy-modulated proton therapy. A plastic tank filled with liquid scintillator was irradiated with pristine proton Bragg peaks. Scintillation light produced during the irradiation was measured with a CCD camera. Acquisition rates of 20 and 10 frames per second (fps) were used to image consecutive frame sequences. These measurements were then compared to ion chamber measurements and Monte Carlo simulations. The light distribution measured from the images acquired at rates of 20 and 10 fps have standard deviations of 1.1% and 0.7%, respectively, in the plateau region of the Bragg curve. Differences were seen between the raw LS signal and the ion chamber due to the quenching effects of the LS and due to the optical properties of the imaging system. The authors showed that this effect can be accounted for and corrected by Monte Carlo simulations. The liquid scintillator detector system has a good potential for performing fast proton beam verification and characterization