International Journal of Particle Therapy最新文献

Purpose: Particle therapy is gaining popularity due to its dosimetric benefits. Particle radiation also has a higher linear energy transfer (LET) than X-rays, leading to more complex DNA damage and a higher relative biological effectiveness (RBE). While potentially beneficial, there remains significant uncertainty in how RBE depends on genetic features of irradiated cells. Understanding how cells respond to and repair these damages is crucial for optimising radiotherapy.

Materials and methods: This study evaluates how loss of different DNA double strand break (DSB) repair genes impacts on radiosensitivity. CRISPR-modified RPE-1 cells were exposed to 6 different LETs using X-rays, protons, carbon ions, and alpha particles, following which clonogenic survival and DNA DSB repair kinetics were measured. Experimental data were then compared with predictions from a mechanistic model of radiation response (Medras).

Results: Clonogenic assays showed that cells lacking ATM and NHEJ repair genes were particularly radiosensitive, even for high LET exposures. While RBE increased with LET for all analysed knockout lines, RBE increased at a slower rate for cells that were more sensitive to X-rays, regardless of the affected pathway. Moreover, data showed no significant difference in DNA repair pathway dependence as a function of LET. Medras-predicted responses were in good agreement with both the genetic background and LET dependencies of radiosensitivity, without any assumption of a change in repair pathway dependence with LET.

Conclusion: This research further highlights the importance of DSB repair pathways, particularly NHEJ, in determining cellular sensitivity to different radiation qualities, but suggests that in this system there is little difference in pathway dependence between X-rays and high-LET radiation. Mechanistic approaches like Medras offer a promising approach to predict radiation responses, to support more personalised and effective cancer treatments based on genetic profiles.

Purpose: Photon radiotherapy is the conventional method in the treatment of bilateral whole-lung metastasis. However, uncertainties, longer delivery times, large lateral penumbra, and motion interplay limit intensity-modulated proton therapy (IMPT)'s use in bilateral lung metastases. To overcome such limitations in IMPT, this study explores the feasibility of using a novel proton therapy technique, Spot-scanning Proton Arc (SPArc) therapy, to improve the dose sparing to the heart and other healthy tissue for this pediatric patient compared to the volumetric modulated arc therapy (VMAT) and IMPT.

Patients and methods: A 13-year-old patient with a malignant neoplasm of bone and articular cartilage, presenting with bilateral whole-lung metastasis, received whole-lung irradiation of 15 Gy in 10 fractions using VMAT. For comparative analysis, plans were generated using IMPT and SPArc.

Results: The study showed that SPArc was superior in sparing the heart and enhancing delivery efficiency compared to both VMAT and IMPT. The mean heart dose was 5.41 Gy for SPArc, 8.48 Gy for IMPT, and 9.56 Gy for VMAT. D50 of the heart was 3.06 Gy for SPArc, 9.13 Gy for IMPT, and 9.12 Gy for VMAT. The integral body dose was 137 Gy·L in VMAT,189 Gy·L in IMPT, and 98 Gy·L in SPArc.

Conclusion: Spot-scanning proton arc demonstrated effective heart sparing and lower body-integral dose for whole-lung irradiation. Delivery simulations suggested improved efficiency compared with IMPT.

Purpose: Proton therapy offers superior conformality in cranial dose distributions, but its sensitivity to anatomical air-tissue interfaces and patient setup variations can compromise dosimetric robustness. Quality assurance computed tomography (QACT) scans can verify these changes, though they increase cumulative dose and workflow burden. There are currently gaps in knowledge about the setup uncertainty margin that could maintain acceptable daily target coverage, organ at risk (OAR) sparing, and QACT frequency requirements.

Materials and methods: A total of 122 adult patients treated for cranial targets between 2019 and 2023 were retrospectively reviewed. Patients were analyzed for adaptive planning rates based on if they had beams passing through the neck or not, and if beams passed through the nasal cavity or not. Twenty patients that did not have beams passing through the neck or nasal cavity were randomly selected and replanned using 2 mm setup uncertainty for robustness compared to the clinically utilized 3 mm setup uncertainty. Synthetic CTs were created for each daily cone beam CT, and the clinical goals were compared against the robustness expectations.

Results: Six patients had adaptive plans, only 2 of which were due to anatomical changes, and both of these patients had beams passing through the nasal cavity. Volumetric clinical goals for the clinical target volume (CTV) were met in 95.7% and 99.6% of 2 and 3 mm plans, respectively. Maximum deviation for 2 mm plans was -0.3%. Clinical goals were met in 99.3% of both 2 and 3 mm plans. All dose differences were below 50 cGy except for 1 patient.

Conclusion: The implementation of a tailored QACT schedule based on beam trajectory and target location is supported, reducing unnecessary imaging without compromising treatment accuracy recommending a single QACT for all patients except those with targets traversing the sinuses or bulky surface targets. A 2 mm setup uncertainty was shown to provide robust target coverage while minimizing OAR dose.

Purpose: Dynamic Spot-scanning Proton Arc (SPArc_-Dynamic) therapy has gained attention for enhancing dosimetric plan quality. However, its full clinical implementation remains under development. As an interim milestone, we developed step-and-shoot arc therapy (SPArc_-step&shoot) for head-neck cancer treatment.

Patients and methods: An in-house spot and energy-layer sparsity optimization algorithm was integrated into a clinical treatment planning system. The algorithm prioritized higher MU-weighted energy layers and spots to ensure delivery efficiency and superior plan quality while meeting machine requirements (≥0.02MU/spot). A Dynamic SPArc simulator calculated delivery times, and a machine-learning-based synthetic CT(synCT) platform monitored dose robustness. In June 2024, a head-neck cancer patient with parotid gland malignancy was treated using SPArc_-step&shoot (6600 cGy[relative biological effectiveness] in 33 fx) with 9 static fields at 20-degree intervals. Comparative plans (SFO-IMPT, SPArc_-Dynamic) were evaluated for dose metrics, delivery times, and adaptive planning.

Results: SPArc_-step&shoot and SPArc_-Dynamic showed similar target coverage and organ-at-risks sparing, and the plan quality is superior to the 3-field SFO-IMPT in the brainstem, oral cavity, and spinal cord sparing. The simulated continuous arc delivery time is 15.9, 6.32, and 4.31 minutes for SPArc_-step&shoot, SFO-IMPT, and SPArc_-Dynamic, respectively. The actual recorded average treatment delivery time for SPArc_-step&shoot in 33 fx is 16.7 ± 1.56 minutes. QA-CT and synCT showed a similar target coverage degradation and perturbation, and a replan was initiated.

Conclusion: The SPArc_-step&shoot therapy was successfully implemented in the clinical settings, and first patient was successfully treated between June and August 2024. The synCT platform serves a critical role in the daily monitoring process as SPArc_-Dynamic might be more sensitive to the patient geometry changes in HNC treatment.

Purpose: Securing insurance authorization for proton therapy remains a challenge for many centers. When health insurance or employer-sponsored health plans deny coverage, Independent Review Organizations (IROs) can review proton therapy cases. However, despite providing an independent review pathway, IROs are often underutilized in securing approvals for care following a denial.

Materials and methods: We analyzed trends in IRO approvals, strategies, and legal procedures using publicly available data from California (CA), Washington (WA), and New York (NY).

Results: The aggregate analysis of the 3 states revealed an IRO average approval rate for proton therapy of 42.1%, with varying trends across states. All 3 states showed increases in IRO approval rates over time, averaging annual increases of +5.0%, +2.3%, and +7.2% for CA, WA, and NY, respectively. Sarcoma showed the highest IRO approval rate at 84.6%, followed by GYN cancers at 55.6% and breast cancer at 51.4%. CNS tumors and lymphomas had moderate approval rates at 44.7% and 40.0% respectively. Head and neck cancers had a 33.3% approval rate, while thoracic malignancies were at 36.8%. The lowest IRO approval rate was seen in prostate cancer at 16.5%. Qualitative analysis revealed that referencing guidelines, discussing published studies, citing trial inclusion, and submitting personalized letters were associated with higher IRO approval rates.

Conclusion: IRO reviews provide a more objective remedy for patients denied care through internal appeals, particularly for plans with historically unfavorable proton policies. Our study demonstrates that IRO appeals provide a valuable pathway to proton therapy access with higher overturn rates improving significantly in recent years. Nearly half of initially denied patients eventually received approval through this process. Proton centers should strategically utilize IRO reviews to increase patient access and improve approval chances.

Purpose: Robustness evaluation is critical for proton beam therapy (PBT) planning, but ideal robustness criteria are not clearly defined. Here, we compared robustness of PBT plans to published intensity-modulated radiation therapy (IMRT)-derived clinical target volume (CTV) robustness benchmarks and assessed the dosimetric impact of meeting IMRT-derived benchmarks on adjacent organs at risk.

Patients and methods: Patients receiving PBT to 70 GyE in 28 fractions to the prostate alone from 2021 to 2022 at our institution were evaluated. PBT plan robustness was evaluated in nominal and worst-case data scenarios for CTV V100%, CTV V95%, rectum V70 Gy, and bladder V60 Gy. Clinically delivered ("Clinical") plans were compared to IMRT-derived worst-case CTV benchmarks. If benchmarks were not met, PBT plans were modified to meet both CTV V100% and V95% goals ("Benchmark" plans). Dosimetric comparisons between Clinical and Benchmark plans used a Wilcoxon signed-rank test with alpha set at 0.05.

Results: Among 32 patients, median age and PSA at diagnosis were 71 years and 6.84 ng/mL, respectively. Most patients had favorable-intermediate risk disease (56.3%). Only 31% of clinical PBT met both worst-case CTV V100% > 90% and CTV V95% > 99% IMRT benchmarks. Plan renormalization (16 patients) or reoptimization (6 patients) resulted in all Benchmark plans meeting worst-case CTV thresholds. For Benchmark plans, nominal rectum V70 Gy increased from 0.72 to 0.92 cm³, and nominal bladder V60 Gy increased from 5.9% to 6.0% (P < .05 for each). Overall plan hot spot between Clinical and Benchmark plans increased from 104.5 to 105.5% (P < .05).

Conclusion: When compared to an IMRT-derived benchmark for robustness coverage, Clinical PBT plans were less robust. However, all PBT plans were successfully modified to meet worst-case CTV benchmark with limited clinically expected impact on organ at risk dosimetry. Consideration should be made to adopt these benchmark criteria for prostate PBT.

Purpose: The spot size of scanned particle beams is of crucial importance for the correct dose delivery and, therefore, plays a significant role in the quality assurance (QA) of pencil beam scanning ion beam therapy.

Materials and methods: This study compares 5 detector types-radiochromic film, ionization chamber (IC) array, flat panel detector, multiwire chamber, and IC-for measuring the spot size of proton and carbon ion beams.

Results: Variations of up to 30% were found between detectors, underscoring the impact of detector choice on QA outcomes. The multiwire chamber consistently measured the smallest spot sizes, attributed to its intrinsic calculation model, while the IC array yielded larger spot sizes due to volume-averaging effects. These discrepancies highlight the necessity of selecting detectors based on QA needs, such as measurement speed, spatial resolution, and data acquisition methods. Digital detectors offer advantages over film-based ones by automating data processing, reducing manual errors, and providing immediate results.

Conclusion: The study concludes that, although a single Gaussian fit is generally sufficient for QA, more sophisticated models might be beneficial for special applications. These findings aim to guide detector selection for ion beam facilities, enhancing QA procedures.

Purpose: We aim to assess the magnetic resonance imaging (MRI)-to-CT deformable image registration (DIR) quality of our treatment planning system in the pelvic region as the first step of an online MRI-guided particle therapy clinical workflow.

Materials and methods: Using 2 different DIR algorithms, ANAtomically CONstrained Deformation Algorithm (ANACONDA), the DIR algorithm incorporated in RayStation, and Elastix, an open-source registration software, we retrospectively assessed the quality of the deformed CT (dCT) generation in the pelvic region for 5 patients. T1- and T2-weighted daily control MRI acquired prior to treatment delivery were used for the DIR. We compared the contours automatically mapped on the dCT against the manual contours on the MRI (ground truth) by calculating the Dice similarity coefficients and mean distances to the agreement for organs at risk, targets, and outer contour. We assessed the dosimetric impact of the DIR on the clinical treatment plans, comparing the dose-volume histograms and the value of the clinical goals achieved for each dCT. The water equivalent path lengths and dose range 80% (R80%) maps were compared by casting on the beams' eye view.

Results: The T1 sequences performed better for the DIR with ANACONDA compared against the T2. ANACONDA's performance agreed with Elastix. The bladder and rectum led to the worst agreement. For the remaining structures analyzed, Dice similarity coefficients above 0.80 were obtained. Maximum median deviations of 7.1 and 2.1 mm were observed for water equivalent path lengths and R80%, respectively, on the PTV.

Conclusion: This work shows a good agreement on the DIR quality achieved with ANACONDA for the structures in the beams' path. By comparing the R80% generated with ANACONDA and Elastix, we give a first quantification of the uncertainties to be considered in an online MRI-guided particle therapy workflow for pelvic treatment.

Purpose: To compare intensity-modulated proton therapy with CyberKnife (CK) therapy for hypo-fractionated treatments of prostate with focal boost, as a first planning study for prostate with dose escalation to a dominant intraprostatic lesion (DIL).

Materials and methods: Ten patients who possess one DIL in their prostate and their CK plans that were used to treat the planning target volume of prostate were chosen. Six of the plans were further escalated to DIL. Intensity-modulated proton therapy plans were created for the patients with robust optimization, accounting for setup and range uncertainties for the clinical target volume (CTV) of prostate. The CK plans were then compared with the proton plans.

Results: In the worst scenario of the robust evaluation, the proton plans reasonably met all objectives and constraints used in CK planning for both CTV coverage and organs-at-risk (OAR) sparing. Under the nominal scenario of the robust optimization, the proton plans produced dosimetric values comparable to those by the CK plans for both CTV and DIL coverage. The average dose to CTV, outside DIL and urethra, was found lower in the proton plans than in the CK plans due to the uncertainties. A similar trend was observed for the dose conformity to CTV. These two findings, however, were not planning objectives. Regarding organs-at-risk sparing, the proton plans in the nominal scenario were comparable to the CK plans for doses >18.125 Gy; for doses below it, the proton performed better. This study offers a basis for a clinical trial of treatment of prostate cancer by proton that may be transferred from the CK system in our center.

Conclusion: The dosimetric objectives and constraints used in the CK plans were achieved with the proton plans.

Purpose: The purpose of this work was to reduce the severity of radiation dermatitis for breast cancer patients receiving pencil beam scanning proton therapy. The hypothesis was that eliminating proton spots (SpotDelete) in the 0.5 cm skin rind would reduce the potentially higher relative biological effectiveness (RBE) known to occur at the Bragg Peak.

Patients and methods: Our center has been using an in-house developed Python script in RayStation since 2021 to remove spots from the skin rind of breast patients. In this work, we retrospectively reviewed the on-treatment visit data from a cohort of breast patients treated with hypofractionation (16 fractions) before this technique (MinDepth) and after (SpotDelete) to acquire the physician-reported radiation dermatitis scores. We evaluated the delivered treatment plans, calculating the linear energy transfer (LET) and applying 3 variable RBE models, Carabe-Fernandez, Wedenberg, and McNamara. An α/β of 10 was assumed for the skin.

Results: In the MinDepth cohort (n = 28), grade 1, 2, and 3 dermatitis accounted for 57%, 36%, and 7% of the cases, respectively. For SpotDelete (n = 27), the incidence rate of grade 1 and 2 acute radiation dermatitis was 67% and 37%, respectively. There were 0 instances of grade 3 dermatitis observed in the SpotDelete cohort. The onset of radiation dermatitis in the SpotDelete cohort was delayed compared to MinDepth, occurring 1 week later in the course of treatment. There was no significant difference in LET or in any of the variable RBE models when analyzing the 0.5 cm skin rind between the cohorts.

Conclusion: Despite the lack of correlation in LET or RBE, SpotDelete has been shown to reduce the severity and onset of radiation dermatitis. Possibly, more research into the α/β for skin and RBE models based on skin cell lines could provide insight into the efficacy of the SpotDelete technique.