International Journal of Particle Therapy最新文献

Purpose: To systematically compare fully automated planning for 36-field discrete proton arc therapy (36PAT) with: (1) intensity-modulated proton therapy (IMPT) with 4- and 6-field clinical beam-angle class solutions (4CS, 6CS), (2) IMPT with patient-specific, computer-optimized beam-angle configurations with 6, 8 or 10 fields (6BAO, 8BAO, 10BAO), and (3) 36-field equiangular ''Utopia'' IMPT (36Utopia; total focus on dosimetric quality, no delivery time considerations) for oropharyngeal cancer patients.

Materials and methods: All automated plan generations were performed with Erasmus-iCycle. An energy layer (EL) reduction algorithm was developed in Erasmus-iCycle to balance plan quality with delivery time in discrete PAT planning. Patient-tailored beam-angle configurations for BAO plans were obtained with the earlier published iCycle-pBAO. In 36Utopia plans, no EL reductions were applied. While beam configurations varied among approaches, all final plans were automatically generated using the published wish-list driven SISS-MCO optimizer with dosimetry-based sparsity-induced spot selection (SISS), followed by multi-criterial spot weight optimization (MCO) and resulting in Pareto-optimality in spot weights. The same wish-list for all delivery approaches prevented planning bias across approaches.

Results: 36PAT plans achieved organs at risk (OAR) doses and normal tissue complication probability (NTCP) approaching 36Utopia plans. Relative to CS plans, 36PAT plans reduced normal tissue dose, decreasing xerostomia and dysphagia NTCPs. Compared to 4CS, 36PAT reduced summed NTCPs for grade 2 toxicity by 6.1%-point (P = .002) and grade 3 by 2.1%-point (P = .002). For 6CS, reductions were 4.7%-point (P = .002) and 1.2%-point (P = .01), respectively. 36PAT plans also outperformed BAO plans with 6 and 8 fields but were comparable to 10BAO in OAR doses and NTCPs for similar EL numbers and Monitor Units (MU).

Conclusion: PAT demonstrated superior dosimetric quality over clinical class solutions for oropharyngeal cancer and approached Utopia. Ten-field IMPT with personalized beam angles could be an alternative to 36-field PAT with similar expected toxicity, ELs and MUs, but a lower number of fields.

Purpose/objectives: Adenoid cystic carcinoma (ACC) of the head and neck is a rare malignancy with a prolonged but infiltrative course, marked by perineural invasion and high risk of local recurrence and distant metastases. The standard of care for head/neck ACC is surgery and postoperative radiation. Definitive radiation is reserved for those with definitive disease. Given the advantage of proton beam to tailor its dose around the tumor while sparing critical tissues, we sought to report our proton experience in the treatment of head/neck ACC.

Materials/methods: We retrospectively analyzed 106 patients treated with definitive or adjuvant proton therapy for ACC from 2012 to 2023. All patients were staged with computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) and were evaluated by a multidisciplinary team. Radiation doses were ≥66 Gy(RBE) adjuvantly and ≥70 Gy(RBE) definitively. Patients were treated using either uniform scanning or pencil beam scanning (PBS) proton therapy. Primary endpoints included overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LRR), assessed using Kaplan-Meier and cumulative incidence methods.

Results: Of 106 patients, 76 were treated postoperatively and 30 definitively. The 5-year OS was 75% overall, 86% for the adjuvant group, and 45% for the definitive group. Five-year PFS was 47% overall, 54% (adjuvant) vs 29% (definitive). Locoregional control at 5 years was 89% overall, with 93% for adjuvant vs 74% for definitive treatment. Toxicities were generally mild, with acute grade ≤2 dermatitis (53%) and mucositis (33%) most common. Chronic toxicities included xerostomia (38%) and temporal lobe necrosis (4%).

Conclusion: Proton therapy for ACC of the head and neck yields excellent locoregional control, particularly in the adjuvant setting, with manageable toxicity. For patients with unresectable disease or those seeking organ preservation, definitive proton therapy remains a viable, durable treatment option. These findings support proton therapy as a preferred modality in head and neck ACC.

[This corrects the article DOI: 10.1016/j.ijpt.2024.100646.].

Purpose: Although carbon-ion radiation therapy (CIRT) creates a sharp dose distribution, inaccurate irradiation positioning may reduce the tumor dose. In pancreatic CIRT, interfractional tumor motion is a factor causing tumor dose reduction. This motion is typically accounted for in the planning target volume, and it cannot provide sufficient margin because the tumor is surrounded by the gastrointestinal tract. Online adaptive radiation therapy (ART) can solve this problem, but other problems such as equipment design and excessive time consumption remain in CIRT. The purpose of this feasibility study was to evaluate the effectiveness of dose matching (DM), which is more convenient than ART in pancreatic CIRT.

Materials and methods: On the in-room computed tomography images, search isocenters were placed 3 dimensionally around the isocenter determined by target matching (TM) at 0.2 cm intervals. The fractional dose distributions were then calculated at each isocenter. The coordinate with the best clinical target volume coverage (CTV V95%) was determined as the DM isocenter. In actual treatment, the use of couch shifting is assumed for irradiation in accordance with the DM isocenter. To evaluate the effectiveness of DM, variations from the initial plan for CTV V95% (ie, ΔCTV V95%) and organ-at-risk (OAR) dose (ΔD_OAR) in bone matching (BM), TM, and DM were compared.

Results: The median ΔCTV V95% values in BM, TM, and DM were -2.18%, -1.39%, and -0.36%, respectively. DM significantly improved CTV V95%. OAR doses were within their limits. Toxicity in DM was considered equivalent to that in BM because the maximum ΔD_OAR in DM was similar to the BM results.

Conclusion: DM significantly improved CTV V95% in pancreatic CIRT within dose constraints of OARs. However, DM should be properly applied by considering treatment efficacy and efficiency. The appropriate use of TM, DM, and online/offline ART is required for each treatment site to improve the target coverage.

Clear cell adenocarcinoma of the uterine cervix is a rare and aggressive subtype of cervical cancer, typically resistant to conventional radiation therapy and lacking dedicated treatment guidelines. We present the case of a young patient with an ataxia telangiectasia mutation and locally advanced disease, who was unfit for brachytherapy following standard chemoradiotherapy and subsequently received a carbon ion radiation therapy boost. This mixed-beam strategy was well tolerated and led to durable local control along with a nodal response, which is suggestive of a possible abscopal effect. These findings underscore the potential of carbon ion radiation therapy in overcoming radioresistance and suggest a contributory role of genetic background in mediating systemic immune effects.

Purpose: Robustness evaluation is routinely used in clinics to ensure the intended dose delivery for intensity-modulated proton therapy (IMPT). Various methods have been proposed, but there is no consensus on which method should be adopted in clinical practice. This study examined various methods within the widely used worst-case approach to provide insights into IMPT plan evaluation.

Materials and methods: We evaluated the robustness of 20 clinical IMPT plans (10 prostate and 10 head and neck). Five robustness evaluation methods were assessed: error-bar dose distribution (ebDD), root-mean-square error dose (RMSED) distribution, voxel-wise worst-case, physical scenario worst-case, and dose-volume histogram (DVH) band. Correlations between these methods were analyzed. Each method was reviewed for their quantitative and qualitative capabilities to identify potential underdosing or overdosing.

Results: Strong correlations were found between ebDD and RMSED, and between voxel-wise worst-case and physical scenario worst-case. The DVH band method provides a straightforward way to assess whether the worst DVH meets plan criteria and to illustrate dose variations but lacks spatial detail to pinpoint areas of potential underdosing or overdosing. The voxel-wise worst-case captures the worst dose distribution across all evaluation metrics, allowing spatial identification of areas of concern within a single distribution. The physical scenario worst-case also pinpoints specific areas of concern but requires individual assessment for each region of interest and evaluation metric, which can be cumbersome. A 3D visualization with ebDD and RMSED highlights regions of dose variation but does not necessarily indicate clinically meaningful impact.

Conclusion: Different robustness evaluation methods offer different types of information. Our study provides valuable insights to help identify an effective and practical approach for clinical practice. Based on our findings, we propose a potential evaluation strategy: use the DVH band derived from physical uncertainty scenarios to assess whether the worst boundary values meet plan evaluation criteria, and, when concerns arise, apply the voxel-wise worst-case dose distribution to localize areas of potential risk.

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.