The PEARL study is a phase 2 multi-centre trial for good prognosis HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) patients, currently open in the UK. PEARL is investigating the ...dosimetric impact of re-planning a radical radiotherapy plan midway through a course of treatment, based upon the biological response of the primary GTV on 18 FDG PET-CT. With the wider availability of proton beam therapy in the form of Intensity Modulated Proton Therapy (IMPT) as a potential option for radiotherapy in the management of OPSCC, in addition to substantial cost implications, improving methods to determine the patients who will benefit most from IMPT is required. The organ sparing benefits of IMPT are well documented. This modelling planning study investigated whether the benefits of proton therapy can be improved by applying biological response-based adaptation as per the PEARL study planning method.
Objectives:
1. Investigate the dosimetric impact of IMPT by comparing mean dose received by swallowing OARs (SWOARs) between non-adaptive VMAT and non-adapted IMPT plans
2. Investigate the dosimetric impact of adaptation by comparing dose received by SWOARs between non-adaptive IMPT and adapted IMPT plans
3. Investigate the relative dosimetric impact of adaptation by comparing dose received by SWOARs between adaptive VMAT and IMPT plans
4. Identify whether adaptation as per the PEARL Study protocol would influence the delta normal tissue complication probability (ΔNTCP) threshold for proton beam therapy funding in The Netherlands
Anonymized patient datasets were used to model VMAT and IMPT plans using RayStation and optimised for SWOARs.
The following plans were generated:
1. 'NON-ADAPTIVE’: Manually planned non-adapted VMAT
2. 'ADAPTIVE’: Manually planned adapted VMAT
3. 'NON-ADAPTIVE_PROTON’: Manually planned non-adapted IMPT
4. 'ADAPTIVE_PROTON’: Manually planned adapted IMPT
NTCP calculations for dysphagia risk we performed using the validated dysphagia model described by Christianen et al (1). Individual calculations were performed on each case comparing adapted and non-adapted VMAT plans to non-adapted IMPT plans to explore whether they reached the threshold for proton beam treatment funding as per The Netherlands scheme. Mean dose to the superior pharyngeal constrictor muscle and the supraglottis was entered into the following calculation:
1/NTCP = (1+e)–s
where s = -6.09 + (mean dose to the superior pharyngeal constrictor muscle x 0.057) + (mean dose to the supraglottis × 0.037)
All cases had a reduction in their total mean dose to SWOARs, adapted as per PEARL, and planned with IMPT. The magnitude of impact was ranked in the same order for all cases, with optimisation reducing the total mean dose the least, and adapted IMPT the most. Cases 1 and 2, and Cases 3 and 4, demonstrated similar total mean dose reductions despite having different degrees of biological GTV reduction on the iPET-CT. Adaptation had the greatest impact on Cases 2 and 3 for both VMAT and IMPT plans. Display omitted
The NTCP differences between non-adaptive VMAT plans and non-adaptive IMPT plans were >10% suggesting these cases would be candidates for IMPT funding as as per the National Indication Protocol Proton therapy (NIPP) - head and neck cancer criteria in The Netherlands.
Whilst primarily limited by the small number of cases, we have demonstrated that IMPT markedly reduces doses to SWOARs compared to VMAT planning in line with widely published studies. We have also demonstrated that adaptation based on the biological response to the tumour after 2 weeks of chemoradiotherapy can further improve the tissue sparing already achieved with IMPT. This is the first study to demonstrate that SWOAR sparing by IMPT can be improved with biological response guided adaptive radiotherapy.
Our results are in line with published data that IMPT can spare many head and neck SWOARs to a greater extent than VMAT in the treatment of oropharyngeal cancers. In the cases studied here, the impact of IMPT on the mean dose to SWOARs was greater than the impact of adaptation, when compared to standard VMAT planning. However, there may be additional dosimetric benefit when IMPT is adapted to tumour response during a course of radiotherapy treatment, particularly dose to more caudal SWOARs.
In this small cohort, adaptation on VMAT plans was unlikely to have affected a decision for IMPT treatment as per the Netherlands NTCP-based algorithm.
Further work with a larger cohort of patients, as well as real-time studies to collect prospective clinical data on xerostomia and dysphagia rates, is required to properly investigate the clinical advantages of adaptive IMPT.
Liquid-lithium-cooled beryllium target as the p-to-n converter Tun, Z.; Yamani, Z.; Huang, X. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
July 2024, Letnik:
1064
Journal Article
Recenzirano
Thermal analysis and neutron moderation simulations were carried out to assess the feasibility and performance of a proton-beam-driven neutron source where the (p,n) conversion target is a cuvette ...made of beryllium and cooled by flowing liquid lithium. Using a prototype model with 5 MeV proton beam energy, the simulations show that this type of target can be highly beneficial in upgrading existing facilities operating with a beryllium target, or in designing new compact neutron sources.
FLASH radiotherapy is the delivery of ultra-high dose rate radiation several orders of magnitude higher than what is currently used in conventional clinical radiotherapy, and has the potential to ...revolutionize the future of cancer treatment. FLASH radiotherapy induces a phenomenon known as the FLASH effect, whereby the ultra-high dose rate radiation reduces the normal tissue toxicities commonly associated with conventional radiotherapy, while still maintaining local tumor control. The underlying mechanism(s) responsible for the FLASH effect are yet to be fully elucidated, but a prominent role for oxygen tension and reactive oxygen species production is the most current valid hypothesis. The FLASH effect has been confirmed in many studies in recent years, both
and
, with even the first patient with T-cell cutaneous lymphoma being treated using FLASH radiotherapy. However, most of the studies into FLASH radiotherapy have used electron beams that have low tissue penetration, which presents a limitation for translation into clinical practice. A promising alternate FLASH delivery method is via proton beam therapy, as the dose can be deposited deeper within the tissue. However, studies into FLASH protons are currently sparse. This review will summarize FLASH radiotherapy research conducted to date and the current theories explaining the FLASH effect, with an emphasis on the future potential for FLASH proton beam therapy.
A new compact superconducting synchrocyclotron single-room proton solution delivers pulsed proton beams to each spot through several irradiation bursts calculated by an iterative layer delivery ...algorithm. Such a mechanism results in a new beam parameter, burst switching time (BST) in the total beam delivery time (BDT) which has never been studied before. In this study, we propose an experimental approach to build an accurate BDT and sequence prediction model for this new proton solution.
Test fields and clinical treatment plans were used to investigate each beam delivery parameter that impacted BDT. The machine delivery log files were retrospectively analyzed to quantitatively model energy layer switching time (ELST), spot switching time (SSWT), spot spill time (SSPT), and BST. A total of 102 clinical IMPT treatment fields' log files were processed to validate the accuracy of the BDT prediction model in comparison with the result from the current commercial system. Interplay effect is also investigated as a clinical application by comparing this new delivery system model with a conventional cyclotron accelerator model.
The study finds that BST depends on the amount of data to be transmitted between two sequential radiation bursts, including a machine irradiation log file of the previous burst and a command file to instruct the proton system to deliver the next burst. The 102 clinical treatment fields showed that the accuracy of each component of the BDT matches well between machine log files and BDT prediction model. More specifically, the difference of ELST, SSWT, SSPT, and BST were (- 3.1 ± 5.7)%, (5.9 ± 3.9)%, (2.6 ± 8.7)%, and (- 2.3 ± 5.3)%, respectively. The average total BDT was about (2.1 ± 3.0)% difference compared to the treatment log files, which was significantly improved from the current commercial proton system prediction (58 ± 15)%. Compared to the conventional cyclotron system, the burst technique from synchrocyclotron effectively reduced the interplay effect in mobile tumor treatment.
An accurate BDT and sequence prediction model was established for this new clinical compact superconducting synchrocyclotron single-room proton solution. Its application could help users of similar facilities better assess the interplay effect and estimate daily patient treatment throughput.
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•Boron doping affects the surface morphology and roughness of the exfoliated silicon samples.•Boron doping affects the aggregation of damage, the width of the damage band, the size ...and density of stick cavities under the same implantation and annealing parameters.•The surface modification after exfoliation is related to the diffusion of hydrogen and the defect evolution at lower temperatures.
Ultra-thin silicons can be obtained using SMART CUT technology, but there is a lack of systematic research on the effect of boron doping. This paper reports the effects of boron doping on surface modification and defect evolution. Monocrystalline silicon samples with different concentrations of boron doping were implanted to 3.5 × 1017H+/cm2 using a 1.52 MeV High Intensity Proton Implanter (HIPI) and annealed at 300, 400, and 550 ℃. The annealed samples were analyzed by non-contact optical profilometry, Raman spectroscopy, SEM, and TEM. The results show that appropriate boron doping can reduce the surface roughness of the exfoliated samples; excessive boron doping leads to a significant increase in surface roughness (∼525 nm) and produces a step-like morphology. Boron doping leads to changes in the type, concentration and dissociation temperature of hydrogenated defects during implantation. These changes result in the width of damage band changes vary with doping concentration. The density and diameter of the hydrogenated extended defects also changed, which results in the surface modification of samples, such as the change of the surface morphology and substrate roughness. In the end of the paper, the paper discusses the correlation between surface morphology and internal damage for different concentrations of boron doping.
Abstract Background As proton beam radiation therapy (PBRT) may allow greater normal tissue sparing when compared with intensity-modulated radiation therapy (IMRT), we compared the dosimetry and ...treatment-related toxicities between patients treated to the ipsilateral head and neck with either PBRT or IMRT. Methods Between 01/2011 and 03/2014, 41 consecutive patients underwent ipsilateral irradiation for major salivary gland cancer or cutaneous squamous cell carcinoma. The availability of PBRT, during this period, resulted in an immediate shift in practice from IMRT to PBRT, without any change in target delineation. Acute toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results Twenty-three (56.1%) patients were treated with IMRT and 18 (43.9%) with PBRT. The groups were balanced in terms of baseline, treatment, and target volume characteristics. IMRT plans had a greater median maximum brainstem (29.7 Gy vs. 0.62 Gy (RBE), P < 0.001), maximum spinal cord (36.3 Gy vs. 1.88 Gy (RBE), P < 0.001), mean oral cavity (20.6 Gy vs. 0.94 Gy (RBE), P < 0.001), mean contralateral parotid (1.4 Gy vs. 0.0 Gy (RBE), P < 0.001), and mean contralateral submandibular (4.1 Gy vs. 0.0 Gy (RBE), P < 0.001) dose when compared to PBRT plans. PBRT had significantly lower rates of grade 2 or greater acute dysgeusia (5.6% vs. 65.2%, P < 0.001), mucositis (16.7% vs. 52.2%, P = 0.019), and nausea (11.1% vs. 56.5%, P = 0.003). Conclusions The unique properties of PBRT allow greater normal tissue sparing without sacrificing target coverage when irradiating the ipsilateral head and neck. This dosimetric advantage seemingly translates into lower rates of acute treatment-related toxicity.
To evaluate proton beam therapy (PBT) in multimodal treatment for locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinus (NPSCC).
The cases in this study included T3 and T4 ...NPSCC without distant metastases that were treated at our center using PBT between July 2003 and December 2020. These cases were classified into 3 groups based on resectability and treatment strategy: surgery followed by postoperative PBT (group A); those indicated to be resectable, but the patient refused surgery and received radical PBT (group B); and those declared unresectable based on the extent of the tumor and treated with radical PBT (group C).
The study included 37 cases, with 10, 9 and 18 in groups A, B and C, respectively. The median follow-up period in surviving patients was 4.4 years (range 1.0-12.3 years). The 4-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 58%, 43% and 58% for all patients; 90%, 70% and 80% in group A, 89%, 78% and 89% in group B; and 24%, 11% and 24% in group C. There were significant differences in OS (p = 0.0028) and PFS (p = 0.009) between groups A and C; and in OS (p = 0.0027), PFS (p = 0.0045) and LC (p = 0.0075) between groups B and C.
PBT gave favorable outcomes in multimodal treatment for resectable locally advanced NPSCC, including surgery followed by postoperative PBT and radical PBT with concurrent chemotherapy. The prognosis for unresectable NPSCC was extremely poor, and reconsideration of treatment strategies, such as more active use of induction chemotherapy, may improve outcomes.
To investigate adverse events (AEs, CTCAE v4.0) and clinical outcomes for proton beam therapy (PBT) reirradiation (reRT) for breast cancer. From 2011 to 2016, 50 patients received PBT reRT for breast ...cancer in the prospective Proton Collaborative Group (PCG) registry. Acute AEs occurred within 180 days from start of reRT. Late AEs began or persisted beyond 180 days. Fisher's exact and Mann‐Whitney rank‐sum tests were utilized. Kaplan‐Meier methods were used to estimate overall survival (OS) and local recurrence‐free survival (LFRS). Median follow‐up was 12.7 months (0‐41.8). Median prior RT dose was 60 Gy (10‐96.7). Median reRT dose was 55.1 Gy (45.1‐76.3). Median cumulative dose was 110.6 Gy (70.6‐156.8). Median interval between RT courses was 103.8 months (5.5‐430.8). ReRT included regional nodes in 84% (66% internal mammary node IMN). Surgery included the following: 44% mastectomy, 22% wide local excision, 6% lumpectomy, 2% reduction mammoplasty, and 26% no surgery. Grade 3 AEs were experienced by 16% of patients (10% acute, 8% late) and were associated with body mass index (BMI) > 30 kg/m2 (P = 0.04), bilateral recurrence (P = 0.02), and bilateral reRT (P = 0.004). All grade 3 AEs occurred in patients receiving IMN reRT (P = 0.08). At 1 year, LRFS was 93%, and OS was 97%. Patients with gross disease at time of PBT trended toward worse 1‐year LRFS (100% without vs. 84% with, P = 0.06). PBT reRT is well tolerated with favorable local control. BMI > 30, bilateral disease, and IMN reRT were associated with grade 3 AEs. Toxicity was acceptable despite median cumulative dose > 110 Gy.
Proton‐beam therapy results in lower doses to the bladder and rectum compared with intensity‐modulated radiation therapy. Despite these dosimetric differences, genitourinary and gastrointestinal ...toxicity is similar.
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