Search Results (28)

Background/Objectives: Photon re-irradiation in previously treated head and neck cancer (HNC) is constrained by cumulative normal-tissue toxicity. Pencil-beam scanning intensity-modulated proton therapy (PBS-IMPT) allows for a sharper dose conformation than conventional photon techniques, which may widen the therapeutic window in previously irradiated tissue. Methods: Sixty-five patients with recurrent or second primary HNC were enrolled in a prospective single-institution registry and re-irradiated with PBS-IMPT between January 2020 and December 2025. Forty-five were treated with radical intent (69.2%), and 20 were treated postoperatively (30.8%), with a median prescribed dose of 66 Gy (RBE) in 30 fractions. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Locoregional control (LRC), adverse events and the prognostic impact of anatomical extent were secondary endpoints. Results: The median follow-up was 9.3 months. The median OS was 17.2 months (95% CI 13.9–NR), with a 12-month rate of 67.1%. The median PFS was 10.1 months and the median LRC was 28.1 months. Central/skull-base involvement was associated with a non-significant trend toward worse OS (14.3 vs. 35.2 months; p = 0.062) and with significantly worse PFS (9.1 vs. 14.7 months; p = 0.037) than peripheral disease, but LRC did not differ between the groups (p = 0.240). Grade ≥ 3 oral mucositis occurred in 7.7%, with no grade 4–5 acute events. Within a median follow-up of 9.3 months, late osteoradionecrosis affected 6.2%, but late toxicity data remain preliminary given the short follow-up. Ninety-two percent of patients completed treatment. Conclusions: PBS-IMPT re-irradiation provided adequate survival with low acute toxicity. T3–T4 stage at re-irradiation was the only variable retaining significance for PFS on multivariable analysis (HR 4.32, 95% CI 1.24–15.13; p = 0.022). The poor survival observed for central/skull-base disease on Kaplan–Meier curves disappeared after T-stage adjustment, indicating the higher concentration of advanced disease in that compartment. Multicentre prospective data and longer follow-up are needed. Full article

Background and objectives: Previous dynamic collimator system (DCS) developments included: (1) hardware construction and commissioning, (2) an accurate dose calculation algorithm, (3) a quality assurance approach, and (4) development of optimization tools for treatment planning. Clinical DCS implementation necessitates efficient treatment plan delivery and fully integrated tools. In this work, a novel algorithm for minimizing treatment time was developed with the goal of reducing the DCS time increase, relative to conventional pencil beam scanning, to one minute or less per beam. In this extensive end-to-end evaluation, treatment plans generated with a modified U.S. Food and Drug Administration (FDA)-cleared treatment planning system were delivered on an Ion Beam Applications (IBA) Proteus Plus proton therapy system, with and without a DCS, to evaluate delivery times and dosimetric accuracy for a relatively large patient dataset, providing evidence of the clinical potential of the approach. Methods: Ten previously treated brain patients were replanned, consisting of both deep-seated central and superficial targets, the latter of which required an external 4 cm polyethylene range shifter. DCS treatments were optimized using a maximum conformity planning technique exploiting per-spot collimator capabilities. An optimization algorithm was incorporated to minimize treatment delivery time by determining the optimal sequencing of spot positions and collimator settings. Plan quality was quantified using conformity and dose-volume histogram (DVH)-based metrics while delivery accuracy was validated through measurements using both patient-specific quality assurance (PSQA) and log file analysis at the Miami Cancer Institute (MCI). Results: The DCS reduced the dose gradient index on average by 26.4% (17.7–37.1%) and the mean dose to the adjacent healthy tissue (within 10 mm of the target) by 19.3% (16.3–26.2%). The average reduction to the mean and maximum dose to the involved optic nerves was 50% (25.7–80.7%) and 18.7%, respectively, and the mean and D_2cc dose to the involved brainstem was reduced by 63.9% (31.5–96.4%) and 60.4% (10.8–99.8%), respectively. PSQA pass rates among DCS-collimated and baseline uncollimated treatments were 99.7% and 99.2%, respectively. DCS treatment fields were delivered within an average of 49 s (32–61 s) from their uncollimated intensity modulated proton therapy (IMPT) counterparts. Average spot position errors were −0.05 ± 0.2 mm and 0.04 ± 0.2 mm for the x- and y-position, respectively. The maximum error in magnitude for collimator positioning was 0.2 mm or less. Conclusions: DCS collimated IMPT treatments can provide significant dosimetric improvements over uncollimated treatments. These highly collimated treatments can be delivered with sufficient accuracy for clinical use while incurring an additional time penalty of around one minute or less per field compared to uncollimated treatments. Full article

Background/Objectives: Traditionally, proton therapy assumes a fixed relative biological effectiveness (RBE) value of 1.1, which can lead to inaccurate dose calculations in treatment planning. This study examines the effect of dynamic arc delivery and pencil beam scanning (PBS) linear energy transfer (LET) optimization on LET-dependent RBE dose escalation to nervous tissue structures in head and neck (H&N) cancer patients undergoing proton beam therapy, utilizing two RBE dose models. Methods: Fifteen head and neck cancer patients previously treated with PBS proton therapy at high risk of nervous tissue toxicity were retrospectively analyzed. Three plans were developed for each patient: PBS, dynamic arc, and PBS with LET optimization. RBE-weighted dose distributions were calculated and compared for all patient plans using a linear LET-weighted model and a tissue-specific α/β-dependent model. LET-dose (LET_d) constraints were systematically tested to determine optimal values for plan quality and efficacy in altering LET spatial distribution in regions of concern. LET-dependent RBE enhancement was calculated for the three different planning methods. Results: Dynamic arc plans increased RBE enhancement when compared to PBS, while LET optimization for PBS consistently reduced RBE-enhanced dose to nervous tissue compared to non-optimized plans for both RBE models. Patient-specific variability in optimization benefit was observed, with the most significant improvements in cases with greater initial RBE enhancement. A maximum LET_d constraint of 2.5 µm/keV above 80% of the maximum structure dose threshold was found to balance plan quality and RBE mitigation. Conclusions: Dynamic arc delivery increased RBE enhancement relative to static PBS. LET optimization successfully modified LET_d spatial distributions to minimize RBE enhancement to nervous tissue structures when compared to non-LET optimized PBS and dynamic arc plans. Patient-specific risk stratification should be used when clinically deploying LET optimization. Full article

Background: RMS is the most common soft tissue sarcoma in children. Pencil beam scanning proton therapy (PBS PT) enables highly conformal dose delivery with reduced exposure to surrounding healthy structures, making it particularly suited for RMS in critical anatomical regions. Long-term clinical outcome data for this new radiation technique are scarce. Purpose: This study reports long-term outcomes and quality of life after PBS PT in children and adolescents with rhabdomyosarcoma (RMS). Methods and Materials: We retrospectively reviewed 114 children and adolescents with RMS (mostly embryonal, n = 100; 87.7%) treated between 2000 and 2020. Their median age was 4.6 years (range, 0.3–18). All received systemic chemotherapy according to prospective protocols. The median total PT dose delivered was 52 Gy (RBE; range, 41.4–64.8). Results: After a median follow-up period of 7.1 years (range, 0.3 to 17 years), we observed 26 failures overall; 21 (80.8%) occurred in-field. The 5-year local control and overall survival were 81.2% and 81%, respectively. The composite endpoint (non-ocular grade ≥3 toxicity- and failure-free survival) counting the first occurrence of any failure (local or distant), death, or non-ocular CTCAE v5.0 grade ≥3 toxicity was 77.3% at 5 years. At the start of PT, parents and children reported a quality of life significantly worse than that of a German normative group, but during the follow-up period, their scores improved to normal values in nearly all domains within two years. Conclusions: Our two decades of experience with PBS PT provide data that reflect good local control rates and minimal late non-ocular grade 3 toxicity. We also show that quality of life returned to normal scores in nearly all domains within 2 years. Children and adolescents with RMS seem to benefit from PBS PT in terms of toxicity and quality of life, but further prospective, multi-institutional comparative trials are needed. Full article

In view of the great need for quality assurance in radiotherapy, this paper proposes a stitching-based detector (SBD) technique and a set of intelligent algorithms that can reconstruct the information of projected particle beams. The reconstructed information includes the intensity, sigma value, and location of the maximum intensity of the beam under test. To verify the effectiveness of the proposed technique and algorithms, this research study adopts the pencil beam scanning (PBS) form of proton beam therapy (PBT) as an example. Through the SBD technique, it is possible to utilize 128 × 128 ionization chambers, which constitute an ionization plate of 25.6 cm², with an acceptable number of 4096 analog-to-digital converters (ADCs) and a resolution of 0.25 mm. Through simulation, the proposed SBD technique and intelligent algorithms are proven to exhibit satisfactory and practical performance. By using two kinds of maximum intensity definitions, sigma values ranging from 10 to 120, and two definitions in an erroneous case, the maximum error rate is found to be 3.95%, which is satisfactorily low. Through analysis, this research study discovers that most errors occur near the symmetrical and peripheral boundaries. Furthermore, lower sigma values tend to aggravate the error rate because the beam becomes more like an ideal particle, which leads to greater imprecision caused by symmetrical sensor structures as its sigma is reduced. However, because proton beams are normally not projected onto the border region of the sensed area, the error rate in practice can be expected to be even lower. Although this research study adopts PBS PBT as an example, the proposed SBD technique and intelligent algorithms are applicable to any type of particle beam reconstruction in the field of radiotherapy, as long as the particles under analysis follow a Gaussian distribution. Full article

Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT. Full article

Beam position uncertainties along the beam trajectory arise from the accelerator, beamline, and scanning magnets (SMs). They can be monitored in real time, e.g., through strip ionization chambers (ICs), and treatments can be paused if needed. Delivery is more reliable and accurate if the beam position is projected from monitored nozzle parameters to the isocenter, allowing for accurate online corrections to be performed. Beam position projection algorithms are also used in post-delivery log file analyses. In this paper, we investigate the four potential algorithms that can be applied to all pencil beam scanning (PBS) nozzles. For some combinations of nozzle configurations and algorithms, however, the projection uses beam properties determined offline (e.g., through beam tuning or technical commissioning). The best algorithm minimizes either the total uncertainty (i.e., offline and online) or the total offline uncertainty in the projection. Four beam position algorithms are analyzed (A1–A4). Two nozzle lengths are used as examples: a large nozzle (1.5 m length) and a small nozzle (0.4 m length). Three nozzle configurations are considered: IC after SM, IC before SM, and ICs on both sides. Default uncertainties are selected for ion chamber measurements, nozzle entrance beam position and angle, and scanning magnet angle. The results for other uncertainties can be determined by scaling these results or repeating the error propagation. We show the propagation of errors from two locations and the SM angle to the isocenter for all the algorithms. The best choice of algorithm depends on the nozzle length and is A1 and A3 for the large and small nozzles, respectively. If the total offline uncertainty is to be minimized (a better choice if the offline uncertainty is not stable), the best choice of algorithm changes to A1 for the small nozzle for some hardware configurations. Reducing the nozzle length can help to reduce the gantry size and make proton therapy more accessible. This work is important for designing smaller nozzles and, consequently, smaller gantries. This work is also important for log file analyses. Full article

Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V_40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for D_max. For the CTV, the FLASH plans resulted in a higher D_max than the clinical plans (116.9% vs. 103.3%). For the rectum, the V_40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT. Full article

Radiation therapy (RT) is an effective treatment for stage IIA and select stage IIB seminomas. However, given the long life expectancy of seminoma patients, there are concerns about the risk of secondary cancers from RT. This study assessed differences in secondary cancer risk for stage II seminoma patients following proton pencil-beam scanning (PBS) and photon VMAT, compared to 3D conformal photon RT. Ten seminoma patients, five with a IIA staging who received 30 GyRBE and five with a IIB staging who received 36 GyRBE, had three RT plans generated. Doses to organs at risk (OAR) were evaluated, and secondary cancer risks were calculated as the Excess Absolute Risk (EAR) and Lifetime Attributable Risk (LAR). PBS reduced the mean OAR dose by 60% on average compared to 3D, and reduced the EAR and LAR for all OAR, with the greatest reductions seen for the bowel, liver, and stomach. VMAT reduced high doses but increased the low-dose bath, leading to an increased EAR and LAR for some OAR. PBS provided superior dosimetric sparing of OAR compared to 3D and VMAT in stage II seminoma cases, with models demonstrating that this may reduce secondary cancer risk. Therefore, proton therapy shows the potential to reduce acute and late side effects of RT for this population. Full article

Background: This study aims to present the feasibility of developing a synchrotron-based proton ultra-high dose rate (UHDR) pencil beam scanning (PBS) system. Methods: The RF extraction power in the synchrotron system was increased to generate 142.4 MeV pulsed proton beams for UHDR irradiation at ~100 nA beam current. The charge per spill was measured using a Faraday cup. The spill length and microscopic time structure of each spill was measured with a 2D strip transmission ion chamber. The measured UHDR beam fluence was used to derive the spot dwell time for pencil beam scanning. Absolute dose distributions at various depths and spot spacings were measured using Gafchromic films in a solid-water phantom. Results: For proton UHDR beams at 142.4 MeV, the maximum charge per spill is 4.96 ± 0.10 nC with a maximum spill length of 50 ms. This translates to an average beam current of approximately 100 nA during each spill. Using a 2 × 2 spot delivery pattern, the delivered dose per spill at 5 cm and 13.5 cm depth is 36.3 Gy (726.3 Gy/s) and 56.2 Gy (1124.0 Gy/s), respectively. Conclusions: The synchrotron-based proton therapy system has the capability to deliver pulsed proton UHDR PBS beams. The maximum deliverable dose and field size per pulse are limited by the spill length and extraction charge. Full article

Purpose: To assess oncological outcomes, toxicities, quality of life (QoL) and sexual health (SH) of low-grade glioma (LGG) patients treated with pencil-beam scanning proton therapy (PBS-PT). Material and methods: We retrospectively analyzed 89 patients with LGG (Neurofibromatosis type 1; n = 4 (4.5%) patients) treated with PBS-PT (median dose 54 Gy (RBE)) from 1999 to 2022 at our institution. QoL was prospectively assessed during PBS-PT and yearly during follow-up from 2015 to 2023, while a cross-sectional exploration of SH was conducted in 2023. Results: Most LGGs (n = 58; 65.2%) were CNS WHO grade 2 and approximately half (n = 43; 48.3%) were located in the vicinity of the visual apparatus/thalamus. After a median follow-up of 50.2 months, 24 (27%) patients presented with treatment failures and most of these (n = 17/24; 70.8%) were salvaged. The 4-year overall survival was 89.1%. Only 2 (2.2%) and 1 (1.1%) patients presented with CTCAE grade 4 and 3 late radiation-induced toxicity, respectively. No grade 5 late adverse event was observed. The global health as a domain of QoL remained stable and comparable to the reference values during PBS-PT and for six years thereafter. Sexual satisfaction was comparable to the normative population. Conclusions: LGG patients treated with PBS-PT achieved excellent long-term survival and tumor control, with exceptionally low rates of high-grade late toxicity, and favorable QoL and SH. Full article

Background: We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. Methodology: In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7–19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0–85.7) years. The bDFS rates and late toxicity profile were evaluated. Results: Median treatment time was 10 (7–38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)—G2: 9.1%; G3: 0.5%; genitourinary (GU)—G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. Conclusion: Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity. Full article

Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V_40Gy/s) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications. Full article

Purpose: The purpose of this study was to report the clinical and patient-reported outcomes of children and adolescents with intracranial meningioma treated with pencil beam scanning proton therapy (PBS-PT). Material and methods: Out of a total cohort of 207 intracranial meningioma patients treated with PBS-PT between 1999 and 2022, 10 (4.8%) were children or adolescents aged < 18 years. Median age was 13.9 years (range, 3.2–17.2). Six (60%) children were treated as primary treatment (postoperative PT, n = 4; exclusive PT, n = 2) and four (40%) at the time of tumor recurrence. Acute and late toxicities were registered according to Common Terminology Criteria of Adverse Events (CTCAE). Quality of life (QoL) before PBS-PT was assessed using PEDQOL questionnaires. Educational, functional, and social aspects after PT were assessed through our in-house developed follow-up surveys. Median follow-up time was 71.1 months (range, 2.5–249.7), and median time to last questionnaire available was 37.6 months (range, 5.75–112.6). Results: Five (50%) children developed local failure (LF) at a median time of 32.4 months (range, 17.7–55.4) after PBS-PT and four (80%) were considered in-field. One patient died of T-cell lymphoma 127.1 months after PBS-PT. Estimated 5-year local control (LC) and overall survival (OS) rates were 19.4% and 100.0%, respectively. Except for one patient who developed a cataract requiring surgery, no grade ≥3 late toxicities were reported. Before PT, patients rated their QoL lower than their parents in most domains. During the first year after PT, one child required educational support, one needed to attend to a special school, one had social problems and another three children required assistance for daily basic activities (DBA). Three years after PT, only one child required assistance for DBA. Conclusions: The outcome of children with intracranial meningioma treated with PBS-PT is in line with other centers who have reported results of radiation therapy delivered to this particular patient group. This therapy provides acceptable functional status profiles with no high-grade adverse radiation-induced events. Full article

Purpose: To investigate the feasibility of using cone-beam computed tomography (CBCT)-derived synthetic CTs to monitor the daily dose and trigger a plan review for adaptive proton therapy (APT) in head and neck cancer (HNC) patients. Methods: For 84 HNC patients treated with proton pencil-beam scanning (PBS), same-day CBCT and verification CT (vfCT) pairs were retrospectively collected. The ground truth CT (gtCT) was created by deforming the vfCT to the same-day CBCT, and it was then used as a dosimetric baseline and for establishing plan review trigger recommendations. Two different synthetic CT algorithms were tested; the corrected CBCT (corrCBCT) was created using an iterative image correction method and the virtual CT (virtCT) was created by deforming the planning CT to the CBCT, followed by a low-density masking process. Clinical treatment plans were recalculated on the image sets for evaluation. Results: Plan review trigger criteria for adaptive therapy were established after closely reviewing the cohort data. Compared to the vfCT, the corrCBCT and virtCT reliably produced dosimetric data more similar to the gtCT. The average discrepancy in D99 for high-risk clinical target volumes (CTV) was 1.1%, 0.7%, and 0.4% and for standard-risk CTVs was 1.8%, 0.5%, and 0.5% for the vfCT, corrCBCT, and virtCT, respectively. Conclusion: Streamlined APT has been achieved with the proposed plan review criteria and CBCT-based synthetic CT workflow. Full article