Modulated Proton Beams Research Articles

LMIC-13. ENCOURAGING EXPERIENCE OF CONCURRENT CARBOPLATIN DURING CRANIOSPINAL IRRADIATION USING IMAGE GUIDED INTENSITY MODULATED PROTON BEAM (IMPT) IN HIGH-RISK EMBRYONAL TUMORS: FIRST REPORT FROM A LOW MIDDLE-INCOME COUNTRY

Abstract BACKGROUND Concurrent carboplatin during craniospinal irradiation (CSI) using photon radiotherapy in High risk (HR) embryonal tumors has been shown to improve the event free survival in select subgroup of patients. Experience of using concurrent carboplatin during CSI using proton therapy is limited. METHOD A retrospective audit was done in Children <18 years from January 2018 to December 2023 diagnosed with HR embryonal tumors who received image guided pencil beam intensity modulated proton beam therapy-based CSI (35Gy/21#) along with concurrent carboplatin 35mg/m2 at least for 15 fractions. The patient demographics, pathological diagnosis, treatment related toxicities and date of follow-up were recorded in predesigned proforma using electronic medical record. RESULTS Twenty children with HR embryonal tumors with median age at diagnosis 5 years (Range: 1-15 years) with M: F ratio of 3:1 were included in the study. Fifteen (75%) of the patients had HR medulloblastoma defined by spinal metastases or HR molecular subtype of which 5 patients had group 3 medulloblastoma (3- leptomeningeal disease at baseline, 2- MYC amplification) while rest had embryonal tumors (3-NOS, 1-Pinealoblastoma and 1-ETMR). Carboplatin was well tolerated, however 12 (60%) patients developed neutropenia requiring daily G-CSF for an average of 5 days. Average time to complete radiotherapy was 45 days with median interruption of 4 days (Range 1-7). Radiotherapy induced toxicities included Grade 3 skin toxicity in 6 (30%) and grade 2 weight loss in 3 (15%). At a median follow up of 14 months (Range: 4-58), the PFS was 80% in the whole cohort while in the Group 3 Medulloblastoma the PFS was only 20% which was statistically significant(p=0.004). CONCLUSIONS Carboplatin along with proton CSI is well tolerated in children with HR embryonal tumors without significant adversities. Experience is encouraging especially in non-group 3 medulloblastoma patients in our cohort of children with HR embryonal tumors.

Bone Marrow Sparing by Intensity Modulated Proton Beam Therapy in Postoperative Irradiation of Gynecologic Malignancies

Bone Marrow Sparing by Intensity Modulated Proton Beam Therapy in Postoperative Irradiation of Gynecologic Malignancies

Feasibility Study of Robust Treatment Planning in VMAT for Head and Neck Cancer

In general, patient positional uncertainty is considered by adding a geometrically expanded margin to clinical target volume (CTV) in photon radiation therapy. However, this method may not be suitable because image-guided radiotherapy is available. In intensity modulated proton beam therapy, robust treatment planning is currently common to take patient positional uncertainty into account in optimization rather than in margins. The purpose of this study is to assess the feasibility of clinical implementation of the method in volumetric modulated arc therapy (VMAT) for head and neck cancer. We quantitatively evaluated whether the plans with the robust optimization (Robust plans) can adequately cover CTV against patients' positional uncertainties and body shape change throughout a treatment course. Ten head and neck cancer patients were chosen, who were treated with PTV-based VMAT plans in our hospital between 2021.5-2022.4. RayStation V10A (RaySearch Laboratories, Stockholm, Sweden) was used for the robust optimization, which was applied to the CTVs with patient positional uncertainty of 5 mm in the 6-axis direction. Dose prescribed to the high- and low-risk CTVs were to 70 and 56 Gy in 35 fractions, respectively. To create the patients' CT images with residual set-up errors and body shape change at the treatment, pseudo simulation-CT images were created by deformable image registration with CBCT and simulation-CT. Dose distribution at the treatment was re-calculated by applying the plan to the pseudo simulation-CT images. The variation of D98 for the high-risk CTV from the time of treatment planning was evaluated on a weekly basis. For comparison, planning target volume (PTV) -based plans (5 mm margin circumference) were created and a similar evaluation was performed. D98 for the high-risk CTV varied between -3∼2% in the robust plan and between -5∼1% in the PTV-based plan during the treatment course. There was no significant difference in the amount of D98 variation between the two plans by t-test, except for one case with hypopharyngeal cancer. In this case, D98 for the high-risk CTV varied within ±1% with the PTV-based plan, whereas the value decreased up to 3% with the robust plan (p < 0.05). This case often had a residual setup error of approximately 5 mm at the sites related to the pitch rotation of head, suggesting that the dose distribution for the robust plan was affected by non-rigid positional errors. Patient weight loss during the treatment period was -3.5±2.4 kg, showing a weak correlation (r = -0.33) with the variation in D98 for the high-risk CTV. The robust treatment planning exhibits comparable CTV coverage to the conventional PTV-based planning against positional uncertainty and body shape change throughout a treatment period. In order to overcome set-up baseline shift by the non-rigid positional errors, re-planning should be recommended. Further planning studies will be conducted to promote clinical implementation of the method.

MO-0676 Monte Carlo calculated kQ factors for ionization chambers in modulated proton beams

MO-0676 Monte Carlo calculated kQ factors for ionization chambers in modulated proton beams

Planned dose of intensity modulated proton beam therapy versus volumetric modulated arch therapy to tooth-bearing regions

BackgroundIntensity modulated proton beam therapy (IMPT) for head and neck cancer offers dosimetric benefits for the organs at risk when compared to photon-based volumetric modulated arch therapy (VMAT). However, limited data exists about the potential benefits of IMPT for tooth-bearing regions.The aim of this study was to compare the IMPT and VMAT radiation dosimetrics of the tooth-bearing regions in head and neck cancer patients. Also, we aimed to identify prognostic factors for a cumulative radiation dose of ≥40 Gy on the tooth-bearing areas, which is considered the threshold dose for prophylactic dental extractions. MethodsA total of 121 head and neck cancer patients were included in this retrospective analysis of prospectively collected data. We compared the average Dmean values of IMPT versus VMAT of multiple tooth-bearing regions in the same patients. Multivariate logistic regression analysis was performed for receiving a cumulative radiation dose of ≥40 Gy to the tooth-bearing regions (primary endpoint) in both VMAT and IMPT. ResultsA lower Dmean was seen after applying IMPT to the tooth-bearing tumour regions (p < 0.001). Regarding VMAT, oral cavity tumours, T3-T4 tumours, molar regions in the mandible, and regions ipsilateral to the tumour were risk factors for receiving a cumulative radiation dose of ≥40 Gy. ConclusionsIMPT significantly reduces the radiation dose to the tooth-bearing regions.

Fabrication of custom oral positioning devices in head and neck proton radiotherapy.

With complex head and neck diseases that closely approximate crucial organs or have advanced spread and cannot be surgically resected, intensity modulated proton beam radiotherapy (IMPT) is favored due to its superior dose targeting through magnetic manipulation of the proton energy. A radiation mask and an oral positioning device (OPD) immobilize craniofacial, cervical, and oral structures for accurate and reliable radiation delivery. Widely available pe-fabricated thermoplastic OPDs are manufactured in standardized forms and materials that unpredictably affect the proton beams' pathways and range. This technique article showcases a workflow that combines of analog and digital dental techniques to produce a customized 3-D printed OPD within 2 appointments. This article is protected by copyright. All rights reserved.

Treatment Tolerability and Toxicity of Postoperative Proton Beam Therapy for Gynecologic Malignancies: Results of the Prospective Phase 2 APROVE Trial

The APROVE study is a prospective one-arm phase-2 study investigating the safety and treatment tolerability of postoperative proton beam therapy in women with uterine cervical or endometrial cancer. In this analysis, we report the primary study endpoint of safety and treatment tolerability as well as toxicity rates and progression-free survival (PFS). 25 patients were treated with postoperative proton beam therapy with a total dose of 45 to 50.4 Gy (RBE) in 5 to 6×1.8 Gy (RBE) fractions weekly using active raster-scanning intensity modulated proton beam therapy (IMPT). Sequential or simultaneous platinum-based chemotherapy was administered if indicated. The primary endpoint was defined as the lack of any acute ≥grade 3 gastrointestinal (GI) or urogenital (GU) toxicity according to the Common Terminology Criteria for Adverse Events v 4.0 or premature treatment abortion. Secondary endpoints were clinical symptoms and toxicity, quality of life, and PFS. All patients completed IMPT according to the protocol, with a median treatment duration of 43 days (range, 33 to 51 days). No patient developed gastrointestinal or genitourinary toxicity ≥grade 3, and the treatment tolerability rate was 100%. Therefore, the null hypothesis H0: Tolerability Rate ≤80% could be rejected in favor of the alternative hypothesis H1: Tolerability rate >80% using an exact binomial test with a one-sided significance level of α=10% (one-sided P value P=.0059). The median follow-up time after the end of IMPT was 25.1 months (range, 20.2 to 50.3 months). 18 of 25 (75%) patients completed the study follow-up of 24 months. 7 patients had progressive disease. Kaplan-Meier-estimated mean PFS was 39.9 months (95% confidence interval: 33.37 to 46.5 months). Postoperative IMPT is a safe treatment option for cervical and endometrial cancer patients, with only low-grade acute and late toxicities. Larger randomized trials are necessary to further assess the potential of IMPT and improve patient selection.

Single-institution clinical experience using robust intensity modulated proton therapy in chordoma and chondrosarcoma of the mobile spine and sacrum: Feasibility and need for plan adaptation

BackgroundDue to its specific physical characteristics, proton irradiation is especially suited for irradiation of chordomas and chondrosarcoma in the axial skeleton. Robust plan optimization renders the proton beam therapy more predictable upon individual setup errors. Reported experience with the planning and delivery of robustly optimized plans in chordoma and chondrosarcoma of the mobile spine and sacrum, is limited. In this study, we report on the clinical use of robustly optimized, intensity modulated proton beam therapy in these patients. MethodsWe retrospectively reviewed patient, treatment and acute toxicity data of all patients with chordoma and chondrosarcoma of the mobile spine and sacrum, treated between 1 April 2019 and 1 April 2020 at our institute. Anatomy changes during treatment were evaluated by weekly cone-beam CTs (CBCT), supplemented by scheduled control-CTs or ad-hoc control-CTs. Acute toxicity was scored weekly during treatment and at 3 months after therapy according to CTCAE 4.0. Results17 chordoma and 3 chondrosarcoma patients were included. Coverage of the high dose clinical target volume was 99.8% (range 56.1–100%) in the nominal and 80.9% (range 14.3–99.6%) in the voxel-wise minimum dose distribution. Treatment plan adaptation was needed in 5 out of 22 (22.7%) plans. Reasons for plan adaptation were either reduced tumor coverage or increased dose to the OAR. ConclusionsRobustly optimized intensity modulated proton beam therapy for chordoma and chondrosarcoma of the mobile spine is feasible. Plan adaptations due to anatomical changes were required in approximately 23 percent of treatment courses.

Near-Surface Dose Correlates With Toxicity in Patients Receiving Pencil Beam Scanning Intensity Modulated Proton Beam Breast Irradiation

Moist desquamation (MD) and breast/chest wall (CW) pain are common, important acute toxicities associated with breast irradiation (RT). In this study, we correlate near-surface dose (NSD) with acute toxicity in patients receiving pencil beam scanning intensity modulated proton breast RT (PBSIMPT).We reviewed thirty-one patients at a single institution who received PBSIMPT for breast cancer. All patients received PBSIMPT for the initial chest wall or whole breast treatment; all but two patients received regional nodal irradiation. 25 patients were treated to 50 Gy in 25 fractions and 6 patients were treated to 42.56 Gy in 16 fractions. Boosts to the lumpectomy cavity or mastectomy scar were delivered with proton, electron, or photon RT. A near-surface rind volume (SR3), which was bound by the skin surface and 3 mm and limited by the breast or chest wall PTV, was generated to be used prospectively during treatment planning to limit near-surface dose while maintaining appropriate PTV coverage. For this analysis, we retrospectively generated two additional near-surface rind volumes, bound by either the skin surface and 5 mm (SR5), or by 5 mm and 10 mm (SR10) from the skin surface. We determined mean SR doses of each patient's composite plan. Skin rind doses were converted to percent of pre-boost prescription dose to account for differences in prescription dose. The presence of any breast/CW MD, and grade 2/3 ("moderate" or "severe") breast/CW pain during RT and within the first two months of RT were recorded. Mann-Whitney U tests were performed to determine correlations between mean SR doses and toxicity endpoints.The mean composite SR3 dose was 4484 cGY (range 4030-5267) for conventionally fractionated patients and 3983 cGY (range 3568-4040) for hypofractionated patients. Five patients (16.1%) experienced MD, and 6 patients (19.3%) experienced grade 2/3 breast/CW pain. Mean composite SR3 dose converted to percent of prescription dose was 94.6% for patients with grade 2 or higher breast or CW pain, compared to 89.6% for those without (P = 0.036). This difference persisted for mean SR5 dose (96.1% versus 91.1%, P = 0.023) and mean SR10 dose (102.4% versus 99.9%, P = 0.012). Patients with MD had a mean SR3 dose of 93.5% versus 91.0% for those without (P = 0.7), and this trend weakened with mean SR5 dose (94.7% versus 92.9%, P = 0.78) and mean SR10 dose (100.7% versus 100.3%, P = 1.0).Higher NSD significantly correlated with increased breast/CW pain. Further analysis with a larger sample size is warranted to explore correlations between NSD and other toxicity endpoints. Optimization of NSD may reduce toxicity in patients receiving PBS IMPT for breast cancer.

3D Dosimetry Based on LiMgPO4 OSL Silicone Foils: Facilitating the Verification of Eye-Ball Cancer Proton Radiotherapy.

A direct verification of the three-dimensional (3D) proton clinical treatment plan prepared for tumor in the eyeball, using the Eclipse Ocular Proton Planning system (by Varian Medical Systems), has been presented. To achieve this, a prototype of the innovative two-dimensional (2D) circular silicone foils, made of a polymer with the embedded optically stimulated luminescence (OSL) material in powder form (LiMgPO4), and a self-developed optical imaging system, consisting of an illuminating light source and a high-sensitive CCD camera has been applied. A specially designed lifelike eyeball phantom has been used, constructed from 40 flat sheet LMP-based silicone foils stacked and placed together behind a spherical phantom made by polystyrene, all to reflect the curvature of the real eyeball. Two-dimensional OSL signals were captured and further analyzed from each single silicone foil after irradiation using a dedicated patient collimator and a 58.8 MeV modulated proton beam. The reconstructed 3D proton depth dose distribution matches very well with the clinical treatment plan, allowing for the consideration of the new OSL system for further 3D dosimetry applications within the proton radiotherapy area.

Technical Note: A simple and fast daily quality assurance solution for modulated scanning proton and carbon ion beams.

A typical ion beam treatment facility has multiple treatment rooms and may treat with more than one ion species, thus requiring a significant quality assurance (QA) effort. The goal of this work was to perform daily QA using a single irradiation per ion species to obtain the beam dosimetry parameters of dose per monitor unit (D/MU), range, and spot position. The X-ray alignment system should also be checked and the entire procedure performed by therapists. This goal was achieved by designing a jig for the Sun Nuclear Daily QA™ 3 device and combining it with specific brass boluses, a standard QA plan, and a cuboid polyethylene phantom for positioning/repositioning tests. The design of the plan used for each ion species delivery ensured that there was no interference between the tests of the various characteristics. The 1-year monitoring results showed the proposed daily QA procedure was reliable and able to reflect each of the specified QA items of the proton and carbon ion beams. To simplify the daily analysis, the tolerances for the D/MU, beam range, and spot position (±1.5%, ±0.3mm, ±1.5mm, respectively) are checked using only the detector readings without the need for additional data processing. The proposed daily QA procedure was clinically implemented in our facility in April 2019 and has run smoothly for the first 2 years of operation. The total daily QA time for the four-room facility decreased from 1 to 1.5h to 30 to 40 min and was achieved not by reducing QA tests but rather by implementing new technology and procedures permitting acquisition of multiple beam information.

Intensity Modulated Proton Beam Therapy versus Volumetric Modulated Arc Therapy for Patients with Nasopharyngeal Cancer: A Propensity Score-Matched Study.

Simple SummaryBased on literature evidence, it is difficult to conclude the advantages and safety of IMPT in patients with NPC. We performed propensity score matching analysis of patients treated with IMPT and VMAT by the same group of physicians within the same institute. Finally, we observed that IMPT reduced the requirement of nasogastric tube insertion and body weight loss during treatment, and the oncologic outcomes were potentially better than that of VMAT. However, IMPT increased the rate of grade III radiation dermatitis. Our current data indicate that IMPT is safe and beneficial as a frontline therapy for patients with NPC.(1) Background: We compared the outcomes of patients with nasopharyngeal carcinoma treated with IMPT and VMAT. (2) Methods: We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMPT (years: 2016–2018) and VMAT (2014–2018). Survival was estimated using the Kaplan–Meier method. Multivariate Cox proportional hazards regression analysis was used to identify the independent predictors of survival. Binary toxicity endpoint analyses were performed using a Cox model and logistic regression. (3) Results: Eighty patients who received IMPT and VMAT were included. The median follow-up time was 24.1 months in the IMPT group. Progression-free survival (PFS) and overall survival (OS) were not statistically different between the two groups but potentially better in IMPT group. In multivariate analysis, advanced N-stage and body weight loss (BWL; >7%) during radiotherapy were associated with decreased PFS. The IMPT group had significantly less requirement for nasogastric (NG) tube placement and BWL during treatment. The mean oral cavity dose was the only predictive factor in stepwise regression analysis, and IMPT required a significantly lower mean dose. However, IMPT increased the grade 3 radiation dermatitis. (4) Conclusions: IMPT is associated with reduced rates of NG tube insertion and BWL through reducing oral mean dose, potentially producing better oncologic outcomes.

Optimization of Field Design in the Treatment of Rectal Cancer with Intensity Modulated Proton Beam Radiation Therapy: How Many Fields Are Needed to Account for Rectal Distension Uncertainty?

PurposePreoperative chemoradiation represents the standard of care in patients with locally advanced rectal cancer. Robustness is often compromised in the setting of proton beam therapy owing to the sensitivity of proton particles to tissue heterogeneity, such as with intestinal gas. The ideal beam arrangement to mitigate the anatomic uncertainty caused by intestinal gas is not well defined. Methods and MaterialsWe developed pencil beam scanning plans using (1) 1-beam posteroanterior (PA) plans, (2) 2-beam with right and left posterior oblique (RPO and LPO) plans, (3) 3-beam with PA and opposed lateral plans, and (4) 5-beam with PA, RPO, LPO, and opposed lateral plans. We created 12 plans with robustness optimization and ran a total of 60 plan evaluations for varying degrees of intestinal gas distension to evaluate which plans would maintain clinical goals to the greatest degree. ResultsA single PA beam resulted in considerable loss of target coverage to the clinical target volume prescribed 50 Gy (volume receiving 100% of the prescribed dose [V100%] < 90%) with rectal distension ≥3 cm in diameter in the short axis. In contrast, the other field designs maintained coverage with up to 5 cm of distension. On plans generated based on a 5-cm distended rectum with air medium, the 1-beam, 3-beam, and 5-beam arrangements resulted in loss of target coverage (V100% < 90%) with rectal contraction ≤3 cm, whereas the 2-beam arrangement maintained coverage to as low as 2 cm. On plans generated based on a 3-cm distension of the rectum, both the 2-beam and 3-beam arrangements maintained V100% > 90% even with collapsed rectum to as low as 1 cm, simulating a patient treatment scenario without any rectal gas. ConclusionsA single PA beam should be avoided when using proton beam therapy for rectal cancer. RPO/LPO and PA/opposed lateral arrangements may both be considered; RPO/LPO is favored to reduce integral dose and avoid beams traversing the hips. In patients for whom the plan CT has rectal distension of ≥3 cm, resimulation or strategies to reduce intestinal gas should be strongly considered.

Dosimetric properties of a newly developed thermoluminescent sheet-type dosimeter for clinical proton beams.

PurposeThis study aimed to evaluate the dosimetric properties of a newly developed thermoluminescent sheet‐type dosimeter (TLD‐sheet) for clinical proton beams.Materials and MethodsThe TLD‐sheet is composed mainly of manganese doped lithium triborate, with a physical size and thickness of 150 mm × 150 mm and 0.15 mm respectively. It is flexible and can be cut freely for usage. The TLD‐sheet has an effective atomic number of 7.3 and tissue‐equivalent properties. We tested the reproducibility, fading effect, dose linearity, homogeneity, energy dependence, and water equivalent thickness (WET) of the TLD‐sheet for clinical proton beams. We conducted tests with both unmodulated and modulated proton beams at energies of 150 and 210 MeV.ResultsThe measurement reproducibility was within 4%, which included the inhomogeneity of the TLD‐sheet. The fading rates were approximately 20% and 30% after 2 and 7 days respectively. The TLD‐sheet showed notable energy dependence in the Bragg peak and distal end of the spread‐out Bragg peak regions. However, the dose–response characteristics of the TLD‐sheet remained linear up to a physical dose of 10 Gy in this study. This linearity was highly superior to those of commonly used radiochromic film. The thin WET of the TLD‐sheet had little effect on the range.ConclusionAlthough notable energy dependences were observed in Bragg peak region, the response characteristics examined in this study, such as reproducibility, fading effects, dose linearity, dose homogeneity and WET, showed that the TLD‐sheet can be a useful and effective dosimetry tool. With its flexible and reusable characteristics, it may also be an excellent in vivo skin dosimetry tool for proton therapy.

TriB-RT: Simultaneous optimization of photon, electron and proton beams

Purpose. To develop a novel treatment planning process (TPP) with simultaneous optimization of modulated photon, electron and proton beams for improved treatment plan quality in radiotherapy. Methods. A framework for fluence map optimization of Monte Carlo (MC) calculated beamlet dose distributions is developed to generate treatment plans consisting of photon, electron and spot scanning proton fields. Initially, in-house intensity modulated proton therapy (IMPT) plans are compared to proton plans created by a commercial treatment planning system (TPS). A triple beam radiotherapy (TriB-RT) plan is generated for an exemplary academic case and the dose contributions of the three particle types are investigated. To investigate the dosimetric potential, a TriB-RT plan is compared to an in-house IMPT plan for two clinically motivated cases. Benefits of TriB-RT for a fixed proton beam line with a single proton field are investigated. Results. In-house optimized IMPT are of at least equal or better quality than TPS-generated proton plans, and MC-based optimization shows dosimetric advantages for inhomogeneous situations. Concerning TriB-RT, for the academic case, the resulting plan shows substantial contribution of all particle types. For the clinically motivated case, improved sparing of organs at risk close to the target volume is achieved compared to IMPT (e.g. myelon and brainstem −37%) at cost of an increased low dose bath (healthy tissue V 10% +22%). In the scenario of a fixed proton beam line, TriB-RT plans are able to compensate the loss in degrees of freedom to substantially improve plan quality compared to a single field proton plan. Conclusion. A novel TPP which simultaneously optimizes photon, electron and proton beams was successfully developed. TriB-RT shows the potential for improved treatment plan quality and is especially promising for cost-effective single-room proton solutions with a fixed beamline in combination with a conventional linac delivering photon and electron fields.

Theoretical and numerical studies of the phase velocity of wakefields in plasma driven by self-modulated proton beams with electron beam seeding

Significant progress has been made in the studies of wakefield excitation in plasma by a self-modulated high energy proton beam in the past decade. The electron beams accelerated up to 2 GeV by using such a wakefield were demonstrated in the AWAKE experiment at CERN in 2018. Aiming at the application of high energy particle accelerators, new ideas have been investigated in recent years, such as seeding the proton beam self-modulation with an electron beam in order to enhance the strength and stability of the wakefield or adding a density transition in the plasma distribution to enhance the phase velocity and the strength of the wakefield. Here in this work, we investigate the effects of electron beam seeding on the phase velocity of the wakefield generated by the modulated proton beam in plasma. The physical mechanisms responsible for the phase velocity change and the roles played by the electron beam seeding are discussed. The theoretical analysis and two-dimensional particle-in-cell simulations show that both the growth rate and the phase velocity of the wakefield generated by the modulated proton beam can be enhanced by the electron beam seeding. The higher the charge density of the electron beam, the more significant the enhancement effects. The effects of electron beam energy and proton beam longitudinal profiles on the increase of phase velocity are also studied. It is shown that the evolution of the electron beam distribution has a significant effect on the seeding self-modulation process, and thus affecting the phase velocity. A self-focusing electron seeding beam can increase the phase velocity of the wakefield even to superluminal while an expanding seeding beam can reduce the phase velocity and destroy the stability of the whole process. This work may benefit the proton beam seeding self-modulation acceleration and its applications.

Microdosimetry of a therapeutic proton beam with a mini-TEPC and a MicroPlus-Bridge detector for RBE assessment

Proton beams are widely used worldwide to treat localized tumours, the lower entrance dose and no exit dose, thus sparing surrounding normal tissues, being the main advantage of this treatment modality compared to conventional photon techniques. Clinical proton beam therapy treatment planning is based on the use of a general relative biological effectiveness (RBE) of 1.1 along the whole beam penetration depth, without taking into account the documented increase in RBE at the end of the depth dose profile, in the Bragg peak and beyond. However, an inaccurate estimation of the RBE can cause both underdose or overdose, in particular it can cause the unfavourable situation of underdosing the tumour and overdosing the normal tissue just beyond the tumour, which limits the treatment success and increases the risk of complications. In view of a more precise dose delivery that takes into account the variation of RBE, experimental microdosimetry offers valuable tools for the quality assurance of LET or RBE-based treatment planning systems. The purpose of this work is to compare the response of two different microdosimetry systems: the mini-TEPC and the MicroPlus-Bridge detector. Microdosimetric spectra were measured across the 62 MeV spread out Bragg peak of CATANA with the mini-TEPC and with the Bridge microdosimeter. The frequency and dose distributions of lineal energy were compared and the different contributions to the spectra were analysed, discussing the effects of different site sizes and chord length distributions. The shape of the lineal energy distributions measured with the two detectors are markedly different, due to the different water-equivalent sizes of the sensitive volumes: 0.85 μm for the TEPC and 17.3 μm for the silicon detector. When the Loncol’s biological weighting function is applied to calculate the microdosimetric assessment of the RBE, both detectors lead to results that are consistent with biological survival data for glioma U87 cells. Both the mini-TEPC and the MicroPlus-Bridge detector can be used to assess the RBE variation of a 62 MeV modulated proton beam along its penetration depth. The microdosimetric assessment of the RBE based on the Loncol’s weighting function is in good agreement with radiobiological results when the 10% biological uncertainty is taken into account.

Intensity Modulated Proton Beam Therapy (IMPT) in CNS and Skull Base Tumors: Prospective Data of 50 Patients With Early Clinical Follow-Up And Patient Reported Outcomes

Intensity Modulated Proton Beam Therapy (IMPT) in CNS and Skull Base Tumors: Prospective Data of 50 Patients With Early Clinical Follow-Up And Patient Reported Outcomes

Therapeutic proton beams: LET, RBE and microdosimetric spectra with gas and silicon detectors

A sealed mini-TEPC able to work in gas-steady modality, a monolithic silicon device composed by a matrix of micrometric cylindrical diodes and a residual energy measurement stage and the silicon MicroPlus Bridge detector were used to perform microdosimetric measurements at the 62 MeV proton clinical SOBP of CATANA at the Southern National Laboratories of INFN (LNS – INFN, Catania, Italy). Measurements were taken at the same different positions in a PMMA phantom, in order to analyse the detector response differences.Finally, a weighting function was applied to the spectra to see if the microdosimetric detectors are able to monitor RBE data for glioma cells (U87) irradiated at six positions along the same modulated 62-MeV proton beam. The results obtained with the three microdosimeters are compared and discussed.

Acute Toxicities and Short-Term Patient Outcomes After Intensity-Modulated Proton Beam Radiation Therapy or Intensity-Modulated Photon Radiation Therapy for Esophageal Carcinoma: A Mayo Clinic Experience

PurposeIntensity modulated proton beam radiation therapy (IMPT) has a clinically significant dosimetric advantage over intensity modulated photon radiation therapy (IMRT) for the treatment of patients with esophageal cancer, particularly for sparing the heart and lungs. We compared acute radiation therapy–related toxicities and short-term clinical outcomes of patients with esophageal cancer who received treatment with IMPT or IMRT. Methods and MaterialsWe retrospectively reviewed the electronic health records of consecutive adult patients with esophageal cancer who underwent concurrent chemoradiotherapy with IMPT or IMRT in the definitive or neoadjuvant setting from January 1, 2014, through June 30, 2018, with additional follow-up data collected through January 31, 2019. Treatment-related toxicities were evaluated per the Common Terminology Criteria for Adverse Events, version 4. Survival outcomes were estimated with the Kaplan-Meier method. ResultsA total of 64 patients (32 per group) were included (median follow-up time: 10 months for IMPT patients vs 14 months for IMRT patients). The most common radiation therapy regimen was 45 Gy in 25 fractions, and 80% of patients received a simultaneous integrated boost to a median cumulative dose of 50 Gy. Similar numbers of IMPT patients (n = 15; 47%) and IMRT patients (n = 18; 56%) underwent surgery (P = .07), with no difference in pathologic complete response rates (IMPT: n = 5; 33% vs IMRT: n = 7; 39%; P = .14). At 1 year, the clinical outcomes also were similar for IMPT and IMRT patients, respectively. Local control was 92% versus 84% (P = .87), locoregional control 92% versus 80% (P = .76), distant metastasis–free survival 87% versus 65% (P = .08), progression-free survival 71% versus 45% (P = .15), and overall survival 74% versus 71% (P = .62). The rate of acute treatment–related grade 3 toxicity was similar between the groups (P = .71). ConclusionsIn our early experience, IMPT is a safe and effective treatment when administered as part of definitive or trimodality therapy. Longer follow-up is required to evaluate the effectiveness of IMPT.