International Journal of Particle Therapy最新文献

Purpose: Finite proton range affords improved dose conformality of radiation therapy when patient regions-of-interest geometries are well characterized. Substantial changes in patient anatomy necessitate re-planning (RP) to maintain effective, safe treatment. Regularly planned verification scanning (VS) is performed to ensure consistent treatment quality. Substantial resources, however, are required to conduct an effective proton plan verification program, which includes but is not limited to, additional computed tomography (CT) scanner time and dedicated personnel: radiation therapists, medical physicists, physicians, and medical dosimetrists.

Materials and methods: Verification scans (VSs) and re-plans (RPs) of 711 patients treated with proton therapy between June 2015 and June 2018 were studied. All treatment RP was performed with the intent to maintain original plan integrity and coverage. The treatments were classified by anatomic site: brain, craniospinal, bone, spine, head and neck (H&N), lung or chest, breast, prostate, rectum, anus, pelvis, esophagus, liver, abdomen, and extremity. Within each group, the dates of initial simulation scan, number of VSs, number of fractions completed at the time of VS, and the frequency of RP were collected. Data were analyzed in terms of rate of RP and individual likelihood of RP.

Results: A total of 2196 VSs and 201 RPs were performed across all treatment sites. H&N and lung or chest disease sites represented the largest proportion of plan modifications in terms of rate of re-plan (RoR: 54% and 58%, respectively) and individual likelihood of RP on a per patient basis (likelihood of RP [RP%]: 46% and 39%, respectively). These sites required RP beyond 4 weeks of treatment, suggesting continued benefit for frequent, periodic VS. Disease sites in the lower pelvis demonstrated a low yield for RP per VS (0.01-0.02), suggesting that decreasing VS frequency, particularly late in treatment, may be reasonable.

Conclusions: A large degree of variation in RoR and individual RP% was observed between anatomic treatment sites. The present retrospective analysis provides data to help develop anatomic site-based VS protocols.

Purpose: In patients treated with chemoradiation for esophageal cancer (EC), randomized trial data demonstrate that proton beam therapy (PBT) reduces toxicities and postoperative complications (POCs) compared with intensity-modulated radiation therapy (IMRT). However, whether radiation therapy modality affects postoperative health care resource utilization remains unknown.

Materials and methods: We examined 287 patients with EC who received chemoradiation (prescribed 50.4 Gy/GyE) followed by esophagectomy, including a real-world observational cohort of 237 consecutive patients treated from 2007 to 2013 with PBT (n = 81) versus IMRT (n = 156); and an independent, contemporary comparison cohort of 50 patients from a randomized trial treated from 2012 to 2019 with PBT (n = 21) versus IMRT (n = 29). Postoperative complications were abstracted from medical records. Health care charges were obtained from institutional claims and adjusted for inflation (2021 dollars). Charge differences (Δ = $PBT - $IMRT) were compared by treatment using adjusted generalized linear models with the gamma distribution.

Results: Baseline PBT versus IMRT characteristics were not significantly different. In the observational cohort, during the neoadjuvant chemoradiation phase, health care charges were higher for PBT versus IMRT (Δ = +$71,959; 95% confidence interval [CI], $62,274-$82,138; P < .001). There was no difference in surgical charges (Δ = -$2234; 95% CI, -$6003 to $1695; P = .26). However, during postoperative hospitalization following esophagectomy, health care charges were lower for PBT versus IMRT (Δ = -$25,115; 95% CI, -$37,625 to -$9776; P = .003). In the comparison cohort, findings were analogous: Charges were higher for PBT versus IMRT during chemoradiation (Δ = +$61,818; 95% CI, $49,435-$75,069; P < .001), not different for surgery (Δ = -$4784; 95% CI, -$6439 to $3487; P = .25), and lower for PBT postoperatively (Δ = -$27,048; 95% CI, -$41,974 to -$5300; P = .02). Lower postoperative charges for PBT were especially seen among patients with any POCs in the contemporary comparison (Δ = -$176,448; 95% CI, -$209,782 to -$78,813; P = .02).

Conclusion: Higher up-front chemoradiation resource utilization for PBT in patients with EC was partially offset postoperatively, moderated by reduction in POC risks. Results extend existing clinical evidence of toxicity reduction with PBT.

Purpose: To compare the late gastrointestinal (GI) and genitourinary toxicities (GU) estimated using multivariable normal tissue complication probability (NTCP) models, between pencil-beam scanning proton beam therapy (PBT) and helical tomotherapy (HT) in patients of high-risk prostate cancers requiring pelvic nodal irradiation (PNI) using moderately hypofractionated regimen.

Materials and methods: Twelve consecutive patients treated with PBT at our center were replanned with HT using the same planning goals. Six late GI and GU toxicity domains (stool frequency, rectal bleeding, fecal incontinence, dysuria, urinary incontinence, and hematuria) were estimated based on the published multivariable NTCP models. The ΔNTCP (difference in absolute NTCP between HT and PBT plans) for each of the toxicity domains was calculated. A one-sample Kolmogorov-Smirnov test was used to analyze distribution of data, and either a paired t test or a Wilcoxon matched-pair signed rank test was used to test statistical significance.

Results: Proton beam therapy and HT plans achieved adequate target coverage. Proton beam therapy plans led to significantly better sparing of bladder, rectum, and bowel bag especially in the intermediate range of 15 to 40 Gy, whereas doses to penile bulb and femoral heads were higher with PBT plans. The average ΔNTCP for grade (G)2 rectal bleeding, fecal incontinence, stool frequency, dysuria, urinary incontinence, and G1 hematuria was 12.17%, 1.67%, 2%, 5.83%, 2.42%, and 3.91%, respectively, favoring PBT plans. The average cumulative ΔNTCP for GI and GU toxicities (ΣΔNTCP) was 16.58% and 11.41%, respectively, favoring PBT. Using a model-based selection threshold of any G2 ΔNTCP >10%, 67% (8 patients) would be eligible for PBT.

Conclusion: Proton beam therapy plans led to superior sparing of organs at risk compared with HT, which translated to lower NTCP for late moderate GI and GU toxicities in patients of prostate cancer treated with PNI. For two-thirds of our patients, the difference in estimated absolute NTCP values between PBT and HT crossed the accepted threshold for minimal clinically important difference.

Mechanism of action: External beam, whether with photons or particles, remains as the most common type of radiation therapy. The main drawback is that radiation deposits dose in healthy tissue before reaching its target. Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when ¹⁰B is irradiated with low-energy (0.0025 eV) thermal neutrons. The resulting ¹⁰B(n,α)⁷Li capture reaction produces high linear energy transfer (LET) α particles, helium nuclei (⁴He), and recoiling lithium-7 (⁷Li) atoms. The short range (5-9 μm) of the α particles limits the destructive effects within the boron-containing cells. In theory, BNCT can selectively destroy malignant cells while sparing adjacent normal tissue at the cellular levels by delivering a single fraction of radiation with high LET particles.

History: BNCT has been around for many decades. Early studies were promising for patients with malignant brain tumors, recurrent tumors of the head and neck, and cutaneous melanomas; however, there were certain limitations to its widespread adoption and use.

Current limitations and prospects: Recently, BNCT re-emerged owing to several developments: (1) small footprint accelerator-based neutron sources; (2) high specificity third-generation boron carriers based on monoclonal antibodies, nanoparticles, among others; and (3) treatment planning software and patient positioning devices that optimize treatment delivery and consistency.

Purpose: This study aimed to determine the integral depth-dose curves and assess the geometric collection efficiency of different detector diameters in proton pencil beam scanning.

Materials and methods: The Varian ProBeam Compact spot scanning system was used for this study. The integral depth-dose curves with a proton energy range of 130 to 220 MeV were acquired with 2 types of Bragg peak chambers: 34070 with 8-cm diameter and 34089 with 15-cm diameter (PTW), multi-layer ionization chamber with 12-cm diameter (Giraffe, IBA Dosimetry), and PeakFinder with 8-cm diameter (PTW). To assess geometric collection efficiency, the integral depth-dose curves of 8- and 12-cm chamber diameters were compared to a 15-cm chamber diameter as the largest detector.

Results: At intermediate depths of 130, 150, 190, and 220 MeV, PTW Bragg peak chamber type 34089 provided the highest integral depth-dose curves followed by IBA Giraffe, PTW Bragg peak chamber type 34070, and PTW PeakFinder. Moreover, PTW Bragg peak chamber type 34089 had increased geometric collection efficiency up to 3.8%, 6.1%, and 3.1% when compared to PTW Bragg peak chamber type 34070, PTW PeakFinder, and IBA Giraffe, respectively.

Conclusion: A larger plane-parallel ionization chamber could increase the geometric collection efficiency of the detector, especially at intermediate depths and high-energy proton beams.

Purpose: Cranial radiation therapy remains an integral component of curative treatment for pediatric patients with brain tumors. Proton beam radiation therapy (PBT) can limit collateral radiation dose to surrounding normal tissue, thus reducing off-target exposure while maintaining appropriate tumor coverage. While PBT offers significant advantages over photon therapy for pediatric patients with intracranial malignancies, cases of brainstem necrosis after PBT have raised concerns that PBT may pose an increased risk of necrosis over photon therapy. We investigated the incidence of brainstem necrosis at our institution in children treated with PBT for intracranial malignancies.

Patients and methods: Patients with pediatric brain tumor treated with passively scattered PBT, using a gantry-mounted, synchrocyclotron single-vault system between 2013 and 2018, were retrospectively reviewed. Inclusion criteria included patients 21 years of age or younger who received a minimum 0.1 cm³ maximum brainstem dose of 50 Gray relative biological effectiveness (GyRBE). Patients were assessed for "central nervous system necrosis" in the brainstem per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US National Cancer Institute, Bethesda, Maryland) criteria.

Results: Fifty-eight patients were included for analysis. The median age was 10.3 years. Twenty-one (36.2%) patients received craniospinal irradiation. Thirty-four (58.6%) patients received chemotherapy. The median prescription radiation dose was 54 GyRBE. Regarding published dosimetric constraints used at 3 separate proton centers, the goal brainstem D50% <52 GyRBE was exceeded in 23 (40%) patients, but the brainstem Dmax <58 GyRBE was not exceeded in any patients. No patient experienced grade ≥2 brainstem injury. One patient demonstrated radiographic changes consistent with grade 1 toxicity. This patient had myeloablative chemotherapy with tandem stem cell rescue before PBT.

Conclusion: Our data demonstrates a low risk of any brainstem injury in children treated with passively scattered PBT using a single-vault synchrocyclotron.

Purpose: Proton beam therapy (PBT) may provide an advantage when planning well-selected patients with extremity soft tissue sarcoma (eSTS), specifically for large, anatomically challenging cases. We analyzed our early experience with PBT on toxicity and outcomes.

Materials and methods: A retrospective study was performed for eSTS treated between June 2016 and October 2020 with pencil beam scanning PBT at 2 institutions. Diagnostic, treatment, and toxicity characteristics were gathered from baseline to last follow-up or death. Wound complications were defined as secondary operations for wound repair (debridement, drainage, skin graft, and muscle flap) or nonoperative management requiring hospitalization. Statistical analysis was performed with R software.

Results: Twenty consecutive patients with a median age 51.5 years (range, 19-78 years) were included. Median follow-up was 13.7 months (range, 1.7-48.1 months). Tumor presentation was primary (n = 17) or recurrent after prior combined modality therapy (n = 3). Tumor location was either lower extremity (n = 16) or upper extremity (n = 4). Radiation was delivered preoperatively in most patients (n = 18). Median pretreatment tumor size was 7.9 cm (range, 1.3 -30.0 cm). The 1-year locoregional control was 100%. Four patients (20%) had developed metastatic disease by end of follow-up. Maximum toxicity for acute dermatitis was grade 2 in 8 patients (40%) and grade 3 in 3 patients (15%). After preoperative radiation and surgical resection, acute wound complications occurred in 6 patients (35%). Tumor size was larger in patients with acute wound complications compared with those without (medians 16 cm, range [12-30.0 cm] vs 6.3 cm, [1.3-14.4 cm], P = .003).

Conclusion: PBT for well selected eSTS cases demonstrated excellent local control and similar acute wound complication rate comparable to historic controls. Long-term follow-up and further dosimetric analyses will provide further insight into potential advantages of PBT in this patient population.

We introduce a custom-made silicone-filled vaginal spacer for use during treatment of female patients receiving pelvic proton radiation therapy. Commercially available vaginal dilators can be purchased as hollow objects; when filled with a media, they can act as a beam stopper and/or tissue spacer while pushing uninvolved vaginal wall away from a high-dose region. Dosimetric advantages of these specifically constructed silicone-filled vaginal spacers were investigated when compared to the unaltered commercially available product or no vaginal spacer in pediatric proton therapy.

Sexual dysfunction is a common toxicity and detrimental for the quality of life of women treated with chemoradiotherapy for anal cancer. Sexual dysfunction occurs because the vagina is closely approximated to the anal canal and typically receives substantial doses of radiation. Strategies for mitigation have largely been focused on posttreatment therapy and symptom management. The use of daily vaginal dilator placement during radiotherapy to mitigate dose to the vagina has been previously explored with modest gains, while proton therapy is under active investigation for the treatment of anal cancer. Use of proton therapy for anal cancer reduces dose to some organs at risk but may inadvertently increase vaginal toxicity if the proton beam terminates in the vaginal tissue. Herein, we present the case histories of 2 women treated for squamous cell carcinoma of the anal canal with the novel combination of intensity-modulated proton therapy and daily vaginal dilator placement to maximally reduce dose to the vagina and protect it from areas of increased energy deposition at the end of the proton range.

Purpose: The purpose of this work is to study the feasibility of using an XRV-124 scintillation detector in measuring the collinearity of the x-ray system and uniform scanning proton beam.

Methods: A brass aperture for Snout 10 was manufactured. The center of the aperture had an opening of 1 cm in diameter (4 cm for the film measurements). The 2D kV x-ray images of the XRV-124 were acquired such that the marker inside the detector is aligned to the imaging isocenter. After obtaining the optimal camera settings, a uniform scanning proton beam was delivered for various ranges (12 g/cm² to 28 g/cm² in step size of 2 g/cm²). For each range, 10 monitor units (MU) of the first layer were delivered to the XRV-124 detector. Collinearity tests were repeated by using EDR2 and EBT3 films following our current quality assurance protocol in practice. The results from the XRV-124 measurements were compared against the collinearity results from EDR2 and EBT3 films.

Results and discussion: The collinearity results were evaluated in the horizontal (x) and vertical (y) directions. The average deviation in collinearity in the x-direction was -0.24 ± 0.30 mm, 0.57 ± 0.39 mm, and -0.27 ± 0.14 mm for EDR2, EBT3, and XRV-124, respectively. In the y-direction, the average deviation was 0.39 ± 0.07 mm, 0.29 ± 0.14 mm, and 0.39 ± 0.03 mm for EDR2, EBT3, and XRV-124, respectively.

Conclusion: The measurement results from the XRV-124 and films are in good agreement. Compared to film, the use of the XRV-124 detector for collinearity measurements in uniform scanning protons is more efficient and provides results in real time.