International Journal of Particle Therapy最新文献

Proton therapy is a promising but controversial treatment in the management of prostate cancer. Despite its dosimetric advantages when compared with photon radiation therapy, its increased cost to patients and insurers has raised questions regarding its value. Multiple prospective and retrospective studies have been published documenting the efficacy and safety of proton therapy for patients with localized prostate cancer and for patients requiring adjuvant or salvage pelvic radiation after surgery. The Particle Therapy Co-Operative Group (PTCOG) Genitourinary Subcommittee intends to address current proton therapy indications, advantages, disadvantages, and cost effectiveness. We will also discuss the current landscape of clinical trials. This consensus report can be used to guide clinical practice and research directions.

Purpose: To assess possible differences in radiation-induced lymphocyte depletion for esophageal cancer patients being treated with the following 3 treatment modalities: intensity-modulated radiation therapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT).

Methods and materials: We used 2 prediction models to estimate lymphocyte depletion based on dose distributions. Model I used a piecewise linear relationship between lymphocyte survival and voxel-by-voxel dose. Model II assumes that lymphocytes deplete exponentially as a function of total delivered dose. The models can be fitted using the weekly absolute lymphocyte counts measurements collected throughout treatment. We randomly selected 45 esophageal cancer patients treated with IMRT, PSPT, or IMPT at our institution (15 per modality) to demonstrate the fitness of the 2 models. A different group of 10 esophageal cancer patients who had received PSPT were included in this study of in silico simulations of multiple modalities. One IMRT and one IMPT plan were created, using our standards of practice for each modality, as competing plans to the existing PSPT plan for each patient. We fitted the models by PSPT plans used in treatment and predicted absolute lymphocyte counts for IMRT and IMPT plans.

Results: Model validation on each modality group of patients showed good agreement between measured and predicted absolute lymphocyte counts nadirs with mean squared errors from 0.003 to 0.023 among the modalities and models. In the simulation study of IMRT and IMPT on the 10 PSPT patients, the average predicted absolute lymphocyte count (ALC) nadirs were 0.27, 0.35, and 0.37 K/μL after IMRT, PSPT, and IMPT treatments using Model I, respectively, and 0.14, 0.22, and 0.33 K/μL using Model II.

Conclusions: Proton plans carried a lower predicted risk of lymphopenia after the treatment course than did photon plans. Moreover, IMPT plans outperformed PSPT in terms of predicted lymphocyte preservation.

Purpose: Periorbital tumor location presents a significant challenge with 3-dimensional conformal radiation therapy or intensity modulated radiation therapy due to high tumor dose needed in the setting of close proximity to orbital structures with lower tolerance. Proton beam therapy (PBT) is felt to be an effective modality in such cases due to its sharp dose gradient.

Materials and methods: We reviewed our institutional PBT registry and identified 17 patients with tumor epicenters within 2 cm of the eye and optic apparatus treated with passive scatter PBT with comparison volumetric arc therapy plans available. Maximum and mean doses to organs at risk of interest, including optic nerves, optic chiasm, lens, eye ball, pituitary, cochlea, lacrimal gland, and surrounding brain, were compared using the paired Wilcoxon signed rank test. Overall survival was determined using the Kaplan-Meier method.

Results: Median age was 67. Median follow-up was 19.7 months. Fourteen patients underwent upfront resection and received postoperative radiation and 3 received definitive radiation. One patient received elective neck radiation, 2 underwent reirradiation, and 3 had concurrent chemotherapy. There was a statistically significant reduction in mean dose to the optic nerves and chiasm, brain, pituitary gland, lacrimal glands, and cochlea as well as in the maximum dose to the optic nerves and chiasm, pituitary gland, lacrimal glands, and cochlea with PBT. The 18-month cumulative incidence of local failure was 19.1% and 1-year overall survival was 80.9%.

Conclusion: Proton beam therapy resulted in significant dose reductions to several periorbital and optic structures compared with volumetric arc therapy. Proton beam therapy appears to be the optimal radiation modality in such cases to minimize risk of toxicity to periorbital organs at risk.

Purpose: Proton therapy precisely delivers radiation to cancers to cause damaging strand breaks to cellular DNA, kill malignant cells, and stop tumor growth. Therapeutic protons also generate short-lived activated nuclei of carbon, oxygen, and nitrogen atoms in patients as a result of atomic transmutations that are imaged by positron emission tomography (PET). We hypothesized that the transition of ¹⁸O to ¹⁸F in an ¹⁸O-substituted nucleoside irradiated with therapeutic protons may result in the potential for combined diagnosis and treatment for cancer with proton therapy.

Materials and methods: Reported here is a feasibility study with a therapeutic proton beam used to irradiate H₂ ¹⁸O to a dose of 10 Gy produced by an 85 MeV pristine Bragg peak. PET imaging initiated >45 minutes later showed an ¹⁸F decay signal with T_1/2 of ∼111 minutes.

Results: The ¹⁸O to ¹⁸F transmutation effect on cell survival was tested by exposing SQ20B squamous carcinoma cells to physiologic ¹⁸O-thymidine concentrations of 5 μM for 48 hours followed by 1- to 9-Gy graded doses of proton radiation given 24 hours later. Survival analyses show radiation sensitization with a dose modification factor (DMF) of 1.2.

Conclusions: These data support the idea of therapeutic transmutation in vitro as a biochemical consequence of proton activation of ¹⁸O to ¹⁸F in substituted thymidine enabling proton radiation enhancement in a cancer cell. ¹⁸O-substituted molecules that incorporate into cancer targets may hold promise for improving the therapeutic window of protons and can be evaluated further for postproton therapy PET imaging.

Purpose: Anatomical changes and patient setup uncertainties during intensity modulated proton therapy (IMPT) of head and neck (HN) cancers demand frequent evaluation of delivered dose. This work investigated a cone-beam computed tomography (CBCT) and deformable image registration based therapy workflow to demonstrate the feasibility of proton dose calculation on synthetic computed tomography (sCT) for adaptive IMPT treatment of HN cancer.

Materials and methods: Twenty-one patients with HN cancer were enrolled in this study, a retrospective institutional review board protocol. They had previously been treated with volumetric modulated arc therapy and had daily iterative CBCT. For each patient, robust optimization (RO) IMPT plans were generated using ±3 mm patient setup and ±3% proton range uncertainties. The sCTs were created and the weekly delivered dose was recalculated using an adaptive dose accumulation workflow in which the planning computed tomography (CT) was deformably registered to CBCTs and Hounsfield units transferred from the planning CT. Accumulated doses from ±3 mm/±3% RO-IMPT plans were evaluated using clinical dose-volume constraints for targets (clinical target volume, or CTV) and organs at risk.

Results: Evaluation of weekly recalculated dose on sCTs showed that most of the patient plans maintained target dose coverage. The primary CTV remained covered by the V95 > 95% (95% of the volume receiving more than 95% of the prescription dose) worst-case scenario for 84.5% of the weekly fractions. The oral cavity accumulated mean dose remained lower than the worst-case scenario for all patients. Parotid accumulated mean dose remained within the uncertainty bands for 18 of the 21 patients, and all were kept lower than RO-IMPT worst-case scenario for 88.7% and 84.5% for left and right parotids, respectively.

Conclusion: This study demonstrated that RO-IMPT plans account for most setup and anatomical uncertainties, except for large weight-loss changes that need to be tracked throughout the treatment course. We showed that sCTs could be a powerful decision tool for adaptation of these cases in order to reduce workload when using repeat CTs.

Purpose: Postprostatectomy radiation improves disease control, but limited data exist regarding outcomes, toxicities, and patient-reported quality of life with proton therapy.

Method and materials: The first 102 patients who were enrolled on an outcome tracking protocol between 2006 and 2017 and treated with double-scattered proton therapy after prostatectomy were retrospectively reviewed. Eleven (11%) received adjuvant radiation, while 91 (89%) received salvage radiation. Seventy-four received double-scattered proton therapy to the prostate bed only. Twenty-eight received a double-scattered proton therapy prostate-bed boost after prostate-bed and pelvic-node treatment. Eleven adjuvant patients received a median dose of 66.6 GyRBE (range, 66.0-70.2). Ninety-one salvage patients received a median dose of 70.2 GyRBE (range, 66.0-78.0). Forty-five patients received androgen deprivation therapy for a median 9 months (range, 1-30). Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0 criteria, and patient-reported quality-of-life data were reviewed.

Results: The median follow-up was 5.5 years (range, 0.8-11.4 years). Five-year biochemical relapse-free and distant metastases-free survival rates were 72% and 91% for adjuvant patients, 57% and 97% for salvage patients, and 57% and 97% overall. Acute and late grade 3 or higher genitourinary toxicity rates were 1% and 7%. No patients had grade 3 or higher gastrointestinal toxicity. Acute and late grade 2 gastrointestinal toxicities were 5% and 2%. The mean values and SDs of the International Prostate Symptom Score, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite bowel function and bother were 7.5 (SD = 5.9), 10.2 (SD = 8.3), 92.8 (SD = 11.1), and 91.2 (SD = 6.4), respectively, at baseline, and 12.1 (SD = 9.1), 10.1 (SD = 6.7), 87.3 (SD = 18), and 86.7 (SD = 13.8) at the 5-year follow-up.

Conclusion: High-dose postprostatectomy proton therapy provides effective long-term biochemical control and freedom from metastasis, with low acute and long-term gastrointestinal and genitourinary toxicity.

Purpose: Whole lung irradiation (WLI) is indicated for certain pediatric patients with lung metastases. This study investigated whether WLI delivered as intensity-modulated proton therapy (IMPT) could significantly spare the heart and breasts when compared with conventional WLI delivered with anteroposterior/posteroanterior photon fields and with intensity-modulated photon therapy (IMRT) WLI.

Materials and methods: Conventional, IMRT, and IMPT plans were generated for 5 patients (aged 5-22 years). The prescription dose was 16.5 GyRBE in 1.5-GyRBE fractions. Conventional plans used 6-MV photons prescribed to the midline and a field-in-field technique to cover the planning target volume (the internal target volume [ITV] + 1 cm). IMRT plans used 6-MV photons with a 7-beam arrangement with dose prescribed to the planning target volume. IMPT plans used scenario-based optimization with 5% range uncertainty and 5-mm positional uncertainty to cover the ITV robustly. Monte Carlo dose calculation was used for all IMPT plans. Doses were compared with paired Student t test.

Results: The ITV Dmean was similar for the IMPT, conventional, and IMRT plans, but the IMPT plans had a lower Dmin and a higher Dmax at tissue interfaces than conventional plans (Dmean ratio: 0.96, P > .05; Dmin ratio: 0.9, P < .001; Dmax ratio: 1.1, P = .014). Dmeans for breast and heart substructures were lower with IMPT plans than with conventional/IMRT plans (heart ratios, 0.63:0.73; left ventricle ratios, 0.61:0.72; right ventricle ratios, 0.45:0.57; left atrium ratios, 0.79:0.85; right atrium ratios, 0.81:0.86; left breast ratios, 0.40:0.51; right breast ratio, 0.46:0.52; all P < .05).

Conclusions: IMPT resulted in comparable ITV coverage and lower mean doses to the heart and breasts when compared with other techniques. Whole lung irradiation delivered as IMPT warrants prospective evaluation in pediatric patients.

Purpose: To investigate dosimetric implications of biodegradable Biozorb (BZ) markers for proton accelerated partial breast irradiation (APBI) plans.

Materials and methods: Six different BZs were placed within in-house breast phantoms to acquire computed tomography (CT) images. A contour correction method with proper mass density overriding for BZ titanium clip and surrounding tissue was applied to minimize inaccuracies found in the CT images in the RayStation planning system. Each breast phantom was irradiated by a monoenergetic proton beam (103.23 MeV and 8×8 cm²) using a pencil-beam scanning proton therapy system. For a range perturbation study, doses were measured at 5 depths below the breast phantoms by using an ionization chamber and compared to the RayStation calculations with 3 scenarios for the clip density: the density correction method (S1: 1.6 g/cm³), raw CT (S2), and titanium density (S3: 4.54 g/cm³). For the local dose perturbation study, the radiographic EDR2 film was placed at 0 and 2 cm below the phantoms and compared to the RayStation calculations. Clinical effects of the perturbations were retrospectively examined with 10 APBI plans for the 3 scenarios (approved by our institutional review board).

Results: In the range perturbation study, the S1 simulation showed a good agreement with the chamber measurements, while excess pullbacks of 1∼2 mm were found in the S2 and S3 simulations. The film study showed local dose shadowing and perturbation by the clips that RayStation could not predict. In the plan study, no significant differences in the plan quality were found among the 3 scenarios. However, substantial range pullbacks were observed for S3.

Conclusion: The density correction method could minimize the dose and range difference between measurement and RayStation prediction. It should be avoided to simply override the known physical density of the BZ clips for treatment planning owing to overestimation of the range pullback.

Purpose: To test our hypothesis that, for young children with intracranial tumors, proton radiotherapy in a high-income country does not reduce the risk of a fatal subsequent malignant neoplasm (SMN) compared with photon radiotherapy in low- and middle-income countries.

Materials and methods: We retrospectively selected 9 pediatric patients with low-grade brain tumors who were treated with 3-dimensional conformal radiation therapy in low- and middle-income countries. Images and contours were deidentified and transferred to a high-income country proton therapy center. Clinically commissioned treatment planning systems of each academic hospital were used to calculate absorbed dose from the therapeutic fields. After fusing supplemental computational phantoms to the patients' anatomies, models from the literature were applied to calculate stray radiation doses. Equivalent doses were determined in organs and tissues at risk of SMNs, and the lifetime attributable risk of SMN mortality (LAR) was predicted using a dose-effect model. Our hypothesis test was based on the average of the ratios of LARs from proton therapy to that of photon therapy ()(H₀: = 1; H _A : < 1).

Results: Proton therapy reduced the equivalent dose in organs at risk for SMNs and LARs compared with photon therapy for which the for the cohort was 0.69 ± 0.10, resulting in the rejection of H₀ (P < .001, α = 0.05). We observed that the younger children in the cohort (2-4 years old) were at a factor of approximately 2.5 higher LAR compared with the older children (8-12 years old).

Conclusion: Our findings suggest that proton radiotherapy has the strong potential of reducing the risk of fatal SMNs in pediatric patients with intracranial tumors if it were made available globally.