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Objective:To validate the feasibility of the gamma analysis method in the study of prescription dose conversion between logistic nanodosimetry model (LNDM) and microdosimetric kinetic model (MKM) basing on the Chinese self-developed model LNDM by applying clinical experiences of National Institute of Radiological Science (NIRS).Methods:Physical dose distributions derived from the MKM- and LNDM-based carbon ion treatment plans were compared via the method of gamma analysis under the open-source treatment planning platform matRad. In this way, the prescribed dose conversion factor between the MKM- and LNDM-based treatment plans was obtained. Using water phantoms, the influence of geometric shape, size, depth of target volume (TV), prescribed dose and field setting on the conversion factor was investigated comprehensively. Moreover, preliminary verification of the acquired conversion factor was conducted on the C-shape model and a case of liver cancer patient.Results:The conversion factor depended on the field setting rather than the TV shape. Under the condition of single field, the conversion factor was positively correlated with the size and depth of TV, and the prescribed dose. Moreover, the conversion factor was successfully verified using the C-shape model and the patient with liver cancer, where the gamma passing rates (2%/2 mm) of the physical dose distribution generated by the MKM and LNDM treatment plans were 92.79% and 91.19%, respectively.Conclusions:The conversion factors (f=D LNDM/D MKM) obtained in this study might provide guidance for the prescribed dose setting during the carbon ion treatment planning based on the LNDM. Besides, the gamma analysis method could be used for the study of the prescribed dose conversion between different models.
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Objective:To compare the adverse reactions, efficacy and survival rate of carbon ion beam irradiation in the elective lymph node (ENI) drainage area of locally advanced non-small cell lung cancer (LA-NSCLC) with relative biological effect (RBE) dose of 48 Gy using 16 and 12 fractions.Methods:A total of 72 patients with pathologically confirmed LA-NSCLC admitted to Wuwei Heavy Ion Center of Gansu Wuwei Tumor Hospital from June 2020 to December 2021 were enrolled and simple randomly divided into groups A and B, with 36 patients in each group. Patients in groups A and B were treated with carbon ion beam irradiation to the lymph node drainage area with 48 Gy (RBE) using 16 and 12 fractions. The acute and chronic adverse reactions, efficacy and survival rate were observed. The survival curve was drawn by Kaplan-Meier method. Difference test was conducted by log-rank test.Results:The median follow-up time was 13.9 (8.8-15.7) months in group A and 14.6 (6.3-15.9) months in group B. Sixteen (44.4%) patients were effectively treated in group A and 9 (25%) patients in group B. Thirty-four (94.4%) cases achieved disease control in group A and 30 (83.3%) cases in group B. Statistical analysis showed that the overall survival rate in group B was similar to that in group A ( χ2=1.192, P=0.275). Comparison of planning parameters between two groups showed CTV volume, D mean, V 5 Gy(RBE), V 20 Gy(RBE) and V 30 Gy(RBE) of the affected lung, cardiac V 20 Gy(RBE), V 30 Gy(RBE) and D mean, esophageal V 30 Gy(RBE), V 50 Gy(RBE), D max and D mean, D max of the trachea and spinal cord had no significant difference (all P>0.05). No grade 3 or 4 adverse reactions occurred in the enrolled patients during treatment and follow-up. No statistical differences were observed in the acute radiation skin reaction ( χ2=5.134, P=0.077), radiation esophagitis ( χ2=1.984, P=0.371), and advanced radiation pneumonia ( χ2=6.185, P=0.103) between two groups. Conclusions:The two dose fractionation modes of carbon ion therapy system are equally safe in the mediastinal lymphatic drainage area of LA-NSCLC, and the adverse reactions are controllable. The long-term efficacy still needs further observation.
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Head and neck tumors often have complex anatomical structures and are adjacent to important organs. Radiation injury caused by conventional radiotherapy technology is the main dose-limiting factor. Carbon ion beam has become the most ideal radiation to replace photon due to its excellent relative biological effect and Bragg peak. By 2019, 32 000 people worldwide have received carbon ion radiotherapy (CIRT). Despite the efficient tumor killing ability of this technology, radiation injury cannot be avoided. This article reviews the types and incidence of moderate to severe radiation injury caused by CIRT in head and neck cancer to provide a comprehensive understanding of the potential risks in CIRT.
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Objective: Radiation-induced sarcoma (RIS), which develops after radiotherapy, occurs as a secondary sarcoma in the irradiated area after a long latency period following radiation exposure.Patient: A 59-year-old man underwent hormone therapy for prostate cancer, followed by proton therapy (74 GyE) four years ago. Positron emission tomography/computed tomography performed 2.5 years later revealed 18F-FDG accumulation in the left pubis. Three years after proton therapy, the patient developed gradually worsening left inguinal pain and visited our department. Imaging revealed bone destruction with a mixture of osteolysis and osteogenesis in the left pubis and the presence of an extraosseous tumor. Following biopsy, the patient was diagnosed with osteosarcoma.Results: A systemic investigation revealed lung metastasis, and chemotherapy was initiated. The lung metastases shrank, and carbon ion radiotherapy (CIRT, 70.4 GyE) was performed on the left pubic lesion after colostomy. Six months after carbon ion radiotherapy, recurrence was observed in the irradiated field, and CIRT was performed again. However, the patient died 22 months after the initial diagnosis because of cancerous pleurisy and pericarditis.Conclusions: Although RIS is rare, it should be actively identified using biopsy to confirm the diagnosis, keeping in mind that it is an important late complication of radiotherapy.
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Glioma is the most common primary malignant brain tumor. Surgery combined with postoperative radiotherapy is the standard treatment, but the outcome is unsatisfactory. Currently, proton and carbon ion, the most advanced radiotherapy technology, offer substantial clinical advantages over the conventional photon therapy in multiple tumors. However, the effect of proton and carbon ion radiotherapy in glioma has not been clarified clearly. This article will elaborate on the basic research and clinical outcomes of proton and carbon ion radiotherapy for glioma.
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@#<b>Objective</b> To analyze the distribution features of the Bragg peak of carbon ion beams in materials using SRIM software, and to explore the use of computed tomography (CT) number to calculate the incident energy of carbon ion beams. <b>Methods</b> SRIM software was used to study the travel of carbon ion beams (100 to 300 MeV/u) in different equivalent materials, and analyze the effects of the incident energy of carbon ion beams and the type and thickness of equivalent materials on the depth of the Bragg peak of carbon ion beams. Origin 2017 was used to analyze the functional relationship between CT number and water-equivalent Bragg peak depth ratio (<i>Di</i>) through data fitting. <b>Results</b> The ratios of the Bragg peak depths in equivalent materials to that in water almost stayed constant with the increase in the incident energy of carbon ion beams. Through the functional relation between CT number and <i>D</i><sub><i>i</i></sub>, the Bragg peak depth of a carbon ion beam of a given energy in an equivalent material could be converted to the equivalent Bragg peak depth in water. <b>Conclusion</b> With the water-equivalent Bragg peak depth ratio <i>D</i><sub><i>i</i></sub> and CT number of different volume units of human tissues, the equivalent Bragg peak depth in water required for the Bragg peak to fall in the tumor can be accurately calculated, which can be used to reversely infer the needed incident energy of carbon ion beams.
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Objective: Primary undifferentiated pleomorphic sarcoma (UPS) of the bone is rare. However, the common sites are the knee and proximal femur and humerus, while spinal involvement is rare. We report a case of primary UPS of the 11th thoracic vertebra, where corpectomy would have been difficult and extensive, treated with carbon ion radiotherapy.Case report: A 76-year-old man presented with an osteolytic tumor of the 11th thoracic vertebra on plain computed tomography (CT). The spinal cord was compressed and displaced posteriorly by the tumor on magnetic resonance imaging (MRI), and extraosseous extension was observed. An incisional biopsy was performed, and primary UPS of the 11th thoracic vertebra was diagnosed pathologically. Total en bloc spondylectomy was considered to be challenging because of the extraosseous extension and the patient’s age; thus, carbon ion radiotherapy (70.4 GyE / 32 fraction) was performed. Denosumab (120 mg) was administered subcutaneously every four weeks. No adjuvant chemotherapy was administered. Four years post-treatment, imaging revealed a compression fracture of the 11th thoracic vertebra, but there was no recurrence.Conclusion: Despite a poor prognosis and an aggressive course of UPS of the spine, the tumor continues to be controlled without local recurrence four years after carbon ion radiotherapy.
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Objective:To evaluate the feasibility and safety of carbon ion radiotherapy (CIRT) in the treatment of muscle-invasive bladder cancer in phase Ⅰ/Ⅱ clinical trials.Methods:Clinical stage T 2-3 patients with muscle-invasive bladder cancer (without distant metastasis) were studied. A three-fraction treatment was applied, including the local irradiation with the dose from 12 Gy to 24 Gy and 11 fractions of whole-bladder irradiation with a dose of 44 Gy. The carbon ion irradiation dose is determined with relative biological effectiveness (RBE) of 3.0. The total dose for bladder tumor was 56-68 Gy in 14 fractions. The primary endpoints included tumor treatment-related side effects, dose-limiting toxicity (DLT) responses, and local control (LC) rate, and the secondary endpoints included progression-free survival (PFS). Results:Nine patients received CIRT of various doses in the clinical trials, with the dose gradually increasing to 68 Gy. The patients did not suffer from DLT response, acute adverse effects of radiation therapy of grade ≥3, and late radiation adverse reactions during follow-up. When the dose to the tumor reached 68 Gy, there were 2 cases of grade 2 acute urogenital tract reaction and 1 case of acute lower gastrointestinal tract symptom. For the group with a dose above 62 Gy, three cases of grade 1 late radiation bladder reaction were observed and their symptoms included urinary frequency and microscopic hematuria. At the end of treatment, hematuria disappeared, dysuria was relieved, and urine red blood cell value significantly decreased for all the patients. Three months and six months after treatment, the LC rates were 100% and 88.9%, respectively, and the objective response rates were both 88.9%. One patient developed local recurrence and was treated with salvage surgery six months after treatment.Conclusions:The preliminary efficacy observation of CIRT in the treatment of muscle-invasive bladder cancer showed significant short-term efficacy, obvious symptom relief, and good tolerability for patients, without DLT. Therefore, CIRT is safe and feasible.
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Objective:To develop a spot scanning carbon ion beam model based on Monte Carlo code FLUKA and verify the accuracy of physical dose.Methods:A geometric model of the treatment nozzle was established in FLUKA. Various parameters such as monoenergy nominal energy, Gaussian energy spectrum distribution, initial spot size, and beam angular distribution in the model were adjusted to match the reference data of integral depth dose (IDD) and in-air spot size measuremed experimentally. Carbon ion beam plans were generated by using the treatment planning system (TPS). The difference in output dose distribution between FLUKA and TPS was compared by the gamma analysis.Results:The differences in Bragg peak width, beam range, and distal falloff width extracted from the IDD curve between the FLUKA model and measured vaues were less than 0.1 mm, with the maximum difference in spot sizes of 0.17 mm. Under the criterion of 2 mm/2% in all the simulations, 2D- and 3D-γ pass rates were all above 95%.Conclusions:An accurate spot scanning carbon beam model was developed based on the Monte Carlo code FLUKA. It has the potential to be used for not only the verification of clinical treatment plans, but also the development of new ion beam therapy equipment and the calculation of biologically effective dose.
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Objective:To establish a local effect model (LEM)-based rectal dose volume histogram (DVH) prediction model in prostate cancer patients treated with carbon ion therapy based on Japanese experience, aiming to provide reference for clinically reducing the incidence of rectal adverse reactions.Methods:The planning CT data of 76 patients with prostate cancer were collected. The microdosimetric kinetic model (MKM) was used for initial planning, and the LEM was selected to recalculate the biological dose based on the same fields to MKM. Then, the geometric features and DVH of the rectum were extracted from the LEM plans. The planning data of 61 cases were used to establish the prediction model with linear regression and the other 15 cases were used for validation.Results:The ratio of the overlapped volume between the rectum and the region of interest (ROI) expended from planning target volume by 1 cm along the left and right directions of the rectum could be proved to be the characteristic parameters for linear regression. The mean goodness-of-fit R2 of predicted and LEM plan-based DVH of 15 cases was 0.964. The results of predicted rectal adverse reactions based on predicted DVH were consistent with those of LEM plan-based DVH. Conclusions:The linear regression method used in this study can establish an accurate prediction model of rectal DVH, which may provide certain reference for reducing the incidence of rectal adverse reactions. Nevertheless, the findings remain to be further verified by clinical trials with larger sample size.
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Objective:A two-dimensional (2D) in-house-built scintillator detection system (SDS) was utilized for quality assurance of the active spot scanning proton and heavy ion accelerator, aiming to establish a rapid detection method and provide reference for the quality of proton and heavy ion beam (spot position, spot size, virtual source-to-axis distance, profile depth dose distribution and beam range).Methods:The SDS consisted of a ceramic gadolinium-sulfoxylate phosphor-scintillating screen, a mirror and a commercial digital camera. The dose distribution image was obtained based on scintillator, mirror reflector and optical signal acquisition device to transform the proton and heavy ion beam into visible light through sulfur gadolinium oxide scintillator and collect visible light information to meet the clinical requirements for the quality of proton and heavy ion beam.Results:The deviation of spot position measured by multifilament proportional chamber and the SDS was less than 1mm. The differences of beam spot size measured by multifilament proportional chamber and the SDS were (1.40±0.59)mm for protons, and (0.5±0.08)mm for carbon ions. For 429.25MeV/u carbon, the virtual source-to-axis distance (V SAD) at the x-and y-axes was 751.8cm and 805.6cm. And difference between physical distance and virtual source-to-axis distance was less than 1%. The range of 287.5MeV/u carbon measured by SDS was 160mm. Conclusions:The in-house-built scintillator detector can measure beam spot position and size, virtual source, depth distribution curve and range, which can be used as an effective tool for quality assurance control of proton and heavy ion therapy.
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Objective:To measure the microdosimetric spectrum of carbon ion beam and calculate the relative biological effect (RBE) distribution, so as to provide reference for radiotherapy microdosimetric research.Methods:A silicon on insulator (SOI) microdosimeter was used to measure the microdosimetric spectrum of 12C ion beam, at 260 MeV/u, provided by Lanzhou Heavy Ion Accelerator National Laboratory. The measured pulse amplitude spectrum was converted to obtain the dose distribution. The microdosimetric spectra and RBE values at different polymethyl methacrylate depths were measured by the combination of different thickness PMMA. Results:The microdosimetric spectra of 12C ion beam at 260 MeV/u were measured at different PMMA depths, and the relationship between dose line energy yD and RBE and different PMMA depths was also obtained. The measurement result showed that the RBE value reached a peak of 2.6 at the PMMA depth of 116.5 mm, and decreased rapidly after the Bragg peak. However, the RBE value was still 1.3 at the trailing point, which was about twice as much as the entrance of the flat zone. Conclusions:This paper provides basic data for carbon ion beam microdosimetric spectroscopy through measurement. The RBE value of 12C ion beam gradually rises and reaches a peak with the increase of PMMA depth. After the Bragg peak position, it drops rapidly, but the biological effect at the tail cannot be ignored. At the same time, it reflects the dose fraction caused by different line energy intervals, and provides a reference for assessing the risk of heavy ion therapy for secondary cancer.
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Compared with conventional high energy X-ray radiotherapy, proton/carbon ion has obvious advantages because of its Bragg peak dose distribution. However, proton heavy ion facility has complex structure, high energy and various radiation types due to various nuclear reaction processes, the radiation protection safety brought by the operation of facilities has gradually attracted attention. Taking the proton/carbon ion radiotherapy facility of Shanghai Proton and Heavy Ion Center as an example, the author mainly analyzed the operation principle of proton/carbon ion treatment facility, the basis of radiation protection, analysis of key radiation source points, etc., so as to provide theoretical support and experience for radiation protection.
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China , Heavy Ion Radiotherapy , Heavy Ions , Occupational Exposure/prevention & control , Protons , Radiation Protection , RadiotherapyABSTRACT
Objective To evaluate the short-term efficacy and toxicities of intensity-modulated carbon ion radiotherapy (IMCT) for patients with locoregionally recurrent nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT).Methods A total of 112 patients with locoregionally recurrent nasopharyngeal carcinoma undergoing salvaging IMCT between May 2015 and February 2018were enrolled in the study.All patients previously received one course of definitive X-ray IMRT.Among them,10 patients (9％) were diagnosed with stage Ⅰ,26 patients (23％) with stage Ⅱ,41 patients (37％) with stage Ⅲ and 35 patients (31％) with stage Ⅳnasopharyngeal carcinoma,respectively.The median age of the cohort was 48 years (range,17-70 years) old.The median dose to the gross tumor volume (GTV) was 60 GyE (range,50-69 GyE).Results With a median follow-up time of 20 months (range,5-45 months),20 patients died and 42 patients developed local recurrence.The 2-year overall survival (OS) and local progression-free survival (LPFS) rates were 85％ and 52％.Both univariate and multivariate analyses demonstrated that stage Ⅳ disease was associated with significantly worse OS.No predictors were found for LPFS.No acute toxicity of grade 3 or higher was observed during reirradiation.Severe (grade 3 or above) late toxicities included xerostomia (n =1),hearing impairment (n =2),temporal lobe injury (n =1) and mucosal necrosis (n =19).Conclusions IMCT is an efficacious and safe treatment for patients with locoregionally recurrent nasopharyngeal carcinoma with acceptable toxicity profile.Long-term follow-up is necessary to further evaluate the long-term efficacy and late toxicities.
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Objective@#To evaluate the dosimetric difference between carbon ion radiotherapy and photon radiotherapy for treating tumors at lacrimal system.@*Methods@#Using the CT images of 10 patients with tumors at lacrimal system, the carbon ion plan, the photon volume intensity modulation plan (VMAT) and the fixed wild photon intensity modulation radiotherapy (IMRT) plan were generated. The prescription was 54 Gy(RBE) in 18 fractions for clinical target volume (CTV) and 63 Gy(RBE) in 18 fractions for CTV-boost. Dosimetric differences of organ at risks were compared based on the same planning target volumes (PTVs) with similar dose coverages.@*Results@#There was no statistically significant difference in the PTV coverage among three plans (P>0.05). Compared to VMAT and IMRT plans, carbon ion plans reduced the mean doses of eyeballs, mean doses and near-maximum doses of optical nerves of both ipsilateral ( t=7.35, 3.79, 4.66, 8.48, 2.52, 2.76, P<0.05) and contralateral eyes (t=3.87, 10.49, 9.16, 4.43, 6.53, 5.12, P<0.05), while the mean dose of brain was decreased from(5.65±3.58) and (5.76±2.09)Gy(RBE) to (0.81±0.90)Gy(RBE) (t=6.76, 17.33, P<0.05).@*Conclusions@#Compared to photon VMAT or IMRT, carbon ion could reduce the doses to optical critical organs around tumors. Thus, carbon ion radiotherapy has potential to reduce patients′ radiation related side-effects.
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Objective To observe the short-term effect and toxicities after carbon ion radiotherapy (CIRT) for tracheal adenoid cystic carcinoma (TACC).Methods From March 2016 to October 2017,a total of 10 patients with TACC were treated using CIRT.Among them,three patients had recurrent disease (two after surgery,and one after brachytherapy),one received bronchoscopic cryosurgery for stage Ⅰ disease,and the other 9 had locally advanced disease (3/6 received endoscopic treatment before CIRT).All patients received CIRT using pencil-beam scanning technique.Except that the patient with recurrent disease after brachytherapy received 60 GyE/20 Fx,the patient received cryosurgery and one recurrent patient after surgery received 66 GyE/22 Fx,all other patients received 69 GyE/23 Fx.Results The median follow-up time was 5.5 (1.5-16.4) months.Among the 9 patients with gross tumors,3 patients achieved complete response,2 achieved partial response,and 4 remained stable disease per RECIST 1.1 criteria.The postcryosurgery patient remained no evidence of disease.Except 1 patient experienced grade 4 tracheal stenosis,no other grade ≥ 3 adverse effects were observed.Grade 2 acute toxicities included 1 hoarseness and 1 neutropenia,both relieved after CIRT.Hypothyroidism in one patient was the only observed grade 2 late toxicity.Conclusion CIRT is safe and effective in the management of TACC during a short-time observation.
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Compared with proton and photon, heavy ion radiotherapy has unique physical and biological advantages, which enables it to kill tumor tissues to the greatest degree and protect surrounding normal tissues as much as possible. Carbon ion is recognized as the most suitable heavy ion for radiotherapy at present. Carbon ion radiotherapy in chordoma, head and neck cancer, non-small cell lung cancer, prostate cancer, cervical cancer and other malignant tumor treatment advantages have been preliminarily reflected. Therefore, understanding the characteristics of carbon ion radiotherapy and its application in tumor therapy will help clinicians make better clinical decisions in the future.
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Objective@#To investigate the effect of lipiodol as embolization agents in liver, after transcatheter arterial chemoembolization, on dose calculation under the carbon ion treatment plan.@*Methods@#The actual relative linear stopping powers(RLSP)in pure lipiodol, pure gel and lipiodol-gel mixture, together with the correctd RLSPs from their CT images, were compared.In seven typical cases with lipiodol deposition area, carbon ion treatment plan was performed for the original lipiodol images.Successively on the basis of analysis that has made, the RLSP in lipiodol deposition area was corrected to be as in normal liver tissue, for which the carbon ion treatment plan was again performed.A comparison was made of differences in water equivalent depth (WED) and dose distribution on different CT images.@*Results@#The RLSP value corrected according to CT image HU value, lipiodol, and lipiodol-gel mixture may increase by 4.6%-139.0% compared with the measured value. In seven typical cases, deposited lipiodol can cause WED to increase by (0.89±0.41) cm along the field track and RBE by(3.83±1.71)Gy within the 1 cm of distal area of target.@*Conclusions@#In order to improve the accuracy of dose distribution calculation, the HU value and/or RLSP in deposited lipiodol area in liver after transcatheter arterial chemoembolization should being corrected to be as in the normal liver tissue.
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Compared with proton and photon,heavy ion radiotherapy has unique physical and biologi-cal advantages,which enables it to kill tumor tissues to the greatest degree and protect surrounding normal tissues as much as possible. Carbon ion is recognized as the most suitable heavy ion for radiotherapy at present. Carbon ion radiotherapy in chordoma,head and neck cancer,non-small cell lung cancer,prostate cancer,cer-vical cancer and other malignant tumor treatment advantages have been preliminarily reflected. Therefore, understanding the characteristics of carbon ion radiotherapy and its application in tumor therapy will help clini-cians make better clinical decisions in the future.
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Objective To evaluate the dosimetric difference between carbon ion radiotherapy and photon radiotherapy for treating tumors at lacrimal system. Methods Using the CT images of 10 patients with tumors at lacrimal system, the carbon ion plan, the photon volume intensity modulation plan ( VMAT) and the fixed wild photon intensity modulation radiotherapy ( IMRT) plan were generated. The prescription was 54 Gy(RBE) in 18 fractions for clinical target volume (CTV) and 63 Gy(RBE) in 18 fractions for CTV-boost. Dosimetric differences of organ at risks were compared based on the same planning target volumes ( PTVs) with similar dose coverages. Results There was no statistically significant difference in the PTV coverage among three plans ( P>0. 05) . Compared to VMAT and IMRT plans, carbon ion plans reduced the mean doses of eyeballs, mean doses and near-maximum doses of optical nerves of both ipsilateral ( t=7. 35, 3. 79, 4. 66, 8. 48, 2. 52, 2. 76, P<0. 05 ) and contralateral eyes ( t=3. 87, 10. 49, 9. 16, 4. 43, 6. 53, 5. 12, P<0. 05), while the mean dose of brain was decreased from(5. 65± 3. 58) and ( 5. 76 ± 2. 09 ) Gy ( RBE ) to ( 0. 81 ± 0. 90 ) Gy ( RBE ) ( t= 6. 76, 17. 33, P<0. 05 ) . Conclusions Compared to photon VMAT or IMRT, carbon ion could reduce the doses to optical critical organs around tumors. Thus, carbon ion radiotherapy has potential to reduce patients' radiation related side-effects.