Comparison of sexual function after robot-assisted radical prostatectomy and carbon-ion radiotherapy for Japanese prostate cancer patients using propensity score matching.

BACKGROUND: The quality of life of patients is an important consideration when selecting treatments for localized prostate cancer (PCa). We retrospectively compared sexual function after robot-assisted radical prostatectomy (RARP) and carbon-ion radiotherapy (CIRT) using propensity score matching. METHODS: In total, 127 Japanese PCa patients treated with RARP and 190 treated with CIRT monotherapy were evaluated. We evaluated the Expanded Prostate Cancer Index Composite (EPIC) score before treatment and 12 and 24 months after treatment. After propensity score matching, data from 101 patients from each group were analyzed. The study protocol was approved by the Institutional Review Board of Gunma University Hospital (no. IRB2020-050, 1839). RESULTS: After propensity score matching, the mean EPIC sexual function summary scores in the RARP and CIRT groups were 46.4 and 48.2, respectively. At 12 and 24 months after treatment, these scores were 27.9 (39.9% decrease) and 28.2 (39.2% decrease) in the RARP group and 41.4 (14.1% decrease) and 41.6 (13.7% decrease) in the CIRT group, respectively. Both groups demonstrated significantly decreased scores after 12 and 24 months of treatment compared to before treatment (all p < 0.05). At 12 and 24 months, the sexual function summary score was significantly higher in the CIRT group than in the RARP group (p < 0.001). CONCLUSIONS: There was a smaller decrease in the EPIC sexual function score in the CIRT group than in the RARP group. These results provide useful information for treatment decision-making of Japanese PCa patients.

Evaluation of the availability of single-position treatment with a rotating gantry and the validity of deformable image registration dose assessment for pancreatic cancer carbon-ion radiotherapy.

BACKGROUND: This study aimed to evaluate the clinical acceptability of rotational gantry-based single-position carbon-ion radiotherapy (CIRT) to reduce the gastrointestinal (GI) dose in pancreatic cancer. We also evaluated the usefulness of the deformable image registration (DIR)-based dosimetry method for CIRT. MATERIAL AND METHODS: Fifteen patients with pancreatic cancer were analyzed. The treatment plans were developed for four beam angles in the supine (SP plan) and prone (PR plan) positions. In the case of using multiple positions, the treatment plan was created with two angles for each of the supine and prone position (SP + PR plan). Dose evaluation for multiple positions was performed in two ways: by directly adding the values of the DVH parameters for each position treatment plan (DVH sum), and by calculating the DVH parameters from the accumulative dose distribution created using DIR (DIR sum). The D2cc and D6cc of the stomach and duodenum were recorded for each treatment plan and dosimetry method and compared. RESULTS: There were no significant differences among any of the treatment planning and dosimetry methods (p > 0.05). The DVH parameters for the stomach and duodenum were higher in the PR plan and SP plan, respectively, and DVH sum tended to be between the SP and PR plans. DVH sum and DIR sum, DVH sum tended to be higher for D2cc and DIR sum tended to be higher for D6cc. CONCLUSION: There were no significant differences in the GI dose, which suggests that treatment with a simple workflow performed in one position should be clinically acceptable. In CIRT, DIR-based dosimetry should be carefully considered because of the potential for increased uncertainty due to the steep dose distributions.

Radiotherapy for Meningioma.

Meningiomas are the most common primary intracranial brain tumor, and have a heterogeneous biology and an unmet need for targeted treatment options. Existing treatments for meningiomas are limited to surgery, radiotherapy, or a combination of these depending on clinical and histopathological features. Treatment recommendations for meningioma patients take into consideration radiologic features, tumor size and location, and medical comorbidities, all of which may influence the ability to undergo complete resection. Ultimately, outcomes for meningioma patients are dictated by extent of resection and histopathologic factors, such as World Health Organization (WHO) grade and proliferation index. Radiotherapy is a critical component of meningioma treatment as either a definitive intervention using stereotactic radiosurgery or external beam radiotherapy, or in the adjuvant setting for residual disease or for adverse pathologic factors, such as high WHO grade. In this chapter, we provide a comprehensive review of radiotherapy treatment modalities, therapeutic considerations, radiation planning, and clinical outcomes for meningioma patients.

A randomized controlled phase III study comparing hadrontherapy with carbon ions versus conventional radiotherapy - including photon and proton therapy - for the treatment of radioresistant tumors: the ETOILE trial.

BACKGROUND: Some cancers such as sarcomas (bone and soft tissue sarcomas) and adenoid cystic carcinomas are considered as radioresistant to low linear energy transfer radiation (including photons and protons) and may therefore beneficiate from a carbon ion therapy. Despite encouraging results obtained in phase I/II trials compared to historical data with photons, the spread of carbon ions has been limited mainly because of the absence of randomized medical data. The French health authorities stressed the importance of having randomized data for carbon ion therapy. METHODS: The ETOILE study is a multicenter prospective randomized phase III trial comparing carbon ion therapy to either advanced photon or proton radiotherapy for inoperable or macroscopically incompletely resected (R2) radioresistant cancers including sarcomas and adenoid cystic carcinomas. In the experimental arm, carbon ion therapy will be performed at the National Center for Oncological Hadrontherapy (CNAO) in Pavia, Italy. In the control arm, photon or proton radiotherapy will be carried out in referent centers in France. The primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival and local control, toxicity profile, and quality of life. In addition, a prospective health-economic study and a radiobiological analysis will be conducted. To demonstrate an absolute improvement in the 5-year PFS rate of 20% in favor of carbon ion therapy, 250 patients have to be included in the study. DISCUSSION: So far, no clinical study of phase III has demonstrated the superiority of carbon ion therapy compared to conventional radiotherapy, including proton therapy, for the treatment of radioresistant tumors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02838602 . Date of registration: July 20, 2016. The posted information will be updated as needed to reflect protocol amendments and study progress.

Neoadjuvant irradiation of extremity soft tissue sarcoma with ions (Extrem-ion): study protocol for a randomized phase II pilot trial.

BACKGROUND: The standard of care treatment for soft tissue sarcoma of the extremities is a wide resection in combination with pre- or postoperative radiotherapy with high local control rates, sparing patients the necessity of amputation without compromising on overall survival rates. The currently preferred timing of radiotherapy is under debate. Albeit having higher rates of acute wound complications, late side effects like fibrosis, joint stiffness or edema are less frequent in preoperative compared to postoperative radiotherapy. This can be explained in smaller treatment volumes and a lower dose in the preoperative setting. Particles allow better sparing of surrounding tissues at risk, and carbon ions additionally offer biologic advantages and are preferred in less radiosensitive tumors. Hypofractionation allows for a significantly shorter treatment duration. METHODS: Extrem-ion is a prospective, randomized, monocentric phase II trial. Patients with resectable or marginally resectable, histologically confirmed soft tissue sarcoma of the extremities will be randomized between neoadjuvant proton or neoadjuvant carbon ion radiotherapy in active scanning beam application technique (39 Gy [relative biological effectiveness, RBE] in 13 fractions [5-6 fractions per week] in each arm). The primary objective is the proportion of therapies without wound healing disorder the first 120 days after surgery or discontinuation of treatment for any reason related to the treatment. The secondary endpoints of the study consist of local control, local progression-free survival, disease-free survival, overall survival, and quality of life. DISCUSSION: The aim of this study is to confirm that hypofractionated, preoperative radiotherapy is safe and feasible. The potential for reduced toxicity by the utilization of particle therapy is the rational of this trial. A subsequent randomized phase III trial will compare the hypofractionated proton and carbon ion irradiation in regards to local control. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04946357 ; Retrospectively registered June 30, 2021.

Changes of the linear energy transfer (LET) and beam width of therapeutic carbon ion beam in density heterogeneous phantoms.

This work aims to investigate the changes in the linear energy transfer (LET) spectra distribution and the beam spot width of a therapeutic carbon ion beam in density heterogeneous phantoms. Three different heterogeneous phantoms were fabricated using a combination of solid water, lung, and bone tissue slabs and irradiated by a single energy carbon beam (276.5 MeV u-1). CR-39 detectors were used for experimental measurements and the Monte Carlo toolkit Geant4 was employed for theoretical simulations. The results demonstrated that the measured LET spectra agree well with the simulation results. The lung and bone tissues displayed no obvious effect on the spectral distribution of LET. The dose-average LET was invariant and showed no obvious difference in the different materials, while the track-average LET increased in the lung and decreased in the bone materials. Similarly, the beam spot size increased in the lung, and decreased in the bone materials. Additionally, the fluence of the secondary fragments varied in different tissues. These findings are expected to provide cross-validation data for the quality assurance of carbon ion therapy and to be beneficial for validating the base data in treatment planning systems.

Systematic review of charged-particle therapy for chordomas and sarcomas of the mobile spine and sacrum.

OBJECTIVE: Long-term local control in patients with primary chordoma and sarcoma of the spine and sacrum is increasingly reliant upon en bloc resection with negative margins. At many institutions, adjuvant radiation is recommended; definitive radiation is also recommended for the treatment of unresectable tumors. Because of the high off-target radiation toxicities associated with conventional radiotherapy, there has been growing interest in the use of proton and heavy-ion therapies. The aim of this study was to systematically review the literature regarding these therapies. METHODS: The PubMed, OVID, Embase, and Web of Science databases were queried for articles describing the use of proton, combined proton/photon, or heavy-ion therapies for adjuvant or definitive radiotherapy in patients with primary sarcoma or chordoma of the mobile spine and sacrum. A qualitative synthesis of the results was performed, focusing on overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS); local control; and postradiation toxicities. RESULTS: Of 595 unique articles, 64 underwent full-text screening and 38 were included in the final synthesis. All studies were level III or IV evidence with a high risk of bias; there was also significant overlap in the reported populations, with six centers accounting for roughly three-fourths of all reports. Five-year therapy outcomes were as follows: proton-only therapies, OS 67%-82%, PFS 31%-57%, and DFS 52%-62%; metastases occurred in 17%-18% and acute toxicities in 3%-100% of cases; combined proton/photon therapy, local control 62%-85%, OS 78%-87%, PFS 90%, and DFS 61%-72%; metastases occurred in 12%-14% and acute toxicities in 84%-100% of cases; and carbon ion therapy, local control 53%-100%, OS 52%-86%, PFS (only reported for 3 years) 48%-76%, and DFS 50%-53%; metastases occurred in 2%-39% and acute toxicities in 26%-48%. There were no studies directly comparing outcomes between photon and charged-particle therapies or comparing outcomes between radiation and surgical groups. CONCLUSIONS: The current evidence for charged-particle therapies in the management of sarcomas of the spine and sacrum is limited. Preliminary evidence suggests that with these therapies local control and OS at 5 years are comparable among various charged-particle options and may be similar between those treated with definitive charged-particle therapy and historical surgical cohorts. Further research directly comparing charged-particle and photon-based therapies is necessary.

Use of Gaussian-type functions for flux-based dose calculations in carbon ion therapy.

In radiation therapy, it is very important to ensure that the radiation dose is correctly delivered to the patient. This is achieved by obtaining quantitative dose measurements for beam calibration in the treatment planning system. Dose calculations should be performed with the required accuracy to a degree of uncertainty of less than 1%. The measurement of the absorbed dose in and around body tissues irradiated with carbon ions requires careful use of materials selected from established phantom and radiation detectors. The main advantage of such materials is that when information on the energy and nature of charged particles at the desired point is incomplete or inaccurate, they can allow determination of the absorbed dose. In general, radiation interactions in a tissue representation caused by carbon ions can be characterized by calculating the linear stopping power. Carbon ions have a limited penetration depth within human tissues that depends on the energy and stopping power of these ions as they penetrate into the body. The purpose of the present study was to calculate the stopping power, range and dose to intestinal and prostate tissues of carbon ions. The stopping power values of these tissues were specified by the effective charge approach method. The 5ZaPa-NR-CV, pcemd-4 and pcSseg-4 sets of Gaussian-type functions were employed for the calculation of electronic charge density. Range calculations were made by means of the Gaussian quadrature method, making use of the continuous slowing down approximation. Flux-based dose calculations were also carried out in accordance with the Bragg-Gray theorem using the Geant4 and FLUKA simulation toolkits. The results were compared with each other and with the SRIM and CasP datasets. Then, depth-dose distributions and range values were verified by positron emission activity using the GATE toolkit. Among the different types of Gaussian functions used here, the best semi-analytical result was found for the 5ZaPa-NR-CV set. The results obtained in the present study can be used for dose verification and dose reconstruction in charged particle radiotherapy and for radiation research on the interaction of radiation with matter. The results calculated here will be useful for quantifying uncertainties associated with stopping power, range, and reconstruction of dose in charged particle therapy.

Performances of the beam monitoring system and quality assurance equipment for the HIMM of carbon-ion therapy.

PURPOSE: The heavy-ion medical machine (HIMM), which is the first commercial medical accelerator designed and built independently by the institute of modern physics (IMP) in Wuwei, Gansu Province, China, had officially completed clinical trials at the time of this article's writing. Three types of detector systems were developed based on the ionization-chamber principle to monitor the beam parameters during treatment in real time, quickly verify the beam performance during a routine checkup, and ensure patient safety. METHODS AND MATERIALS: The above-mentioned detector systems were used for beam monitoring and quality assurance in the treatment system. The beam-monitoring system is composed of three integral ionization chambers (ICs) and two multistrip ionization chambers (MSICs) as a redundant design. The irradiation dose, beam position, and homogeneity of a lateral profile are monitored online by the beam-monitoring system, and safety interlocks are established to keep the test results under the predefined tolerance limitation. The quality-assurance equipment was composed of one MSIC and one IC stack. The IC stack was used for energy verification. RESULTS: The off-axis response of ICs is within a tolerance of 2%, and the dose interlock system (DIS) response time is less than 7 ms during the treatment process. The positioning resolution of MSICs reached 73 µm. The IC stack can verify the beam range within one spill and the measurement resolution is less than 0.2 mm. CONCLUSIONS: The beam-monitoring system (BMS) and quality-assurance equipment (QAE) have been installed and run successfully within HIMM for two years and are associated with the HIMM treatment system to deliver the right dose to the correct position precisely. Furthermore, the daily QA task is simplified by it. Above all, the system has passed the performance test of the China Food and Drug Administration (CFDA).

Immunomodulatory Effects of Radiotherapy.

Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.

Single fraction carbon ion radiotherapy for colorectal cancer liver metastasis: A dose escalation study.

Prognosis is usually grim for those with liver metastasis from colorectal cancer (CRC) who cannot receive resection. Radiation therapy can be an option for those unsuitable for resection, with carbon ion radiotherapy (CIRT) being more effective and less toxic than X-ray due to its physio-biological characteristics. The objective of this study is to identify the optimal dose of single fraction CIRT for colorectal cancer liver metastasis. Thirty-one patients with liver metastasis from CRC were enrolled in the present study. Twenty-nine patients received a single-fraction CIRT, escalating the dose from 36 Gy (RBE) in 5% to 10% increments until unacceptable incidence of dose-limiting toxicity was observed. Dose-limiting toxicity was defined as grade ≥3 acute toxicity attributed to radiotherapy. The prescribed doses were as follows: 36 Gy (RBE) (3 cases), 40 Gy (2 cases), 44 Gy (4 cases), 46 Gy (6 cases), 48 Gy (3 cases), 53 Gy (8 cases) and 58 Gy (3 cases). Dose-limiting toxicity was not observed, but late grade 3 liver toxicity due to biliary obstruction was observed in 2 patients at 53 Gy (RBE). Both cases had lesions close to the hepatic portal region, and, therefore, the dose was escalated to 58 Gy (RBE), limited to peripheral lesions. The 3-year actuarial overall survival rate of all 29 patients was 78%, and the median survival time was 65 months. Local control improved significantly at ≥53 Gy (RBE), with a 3-year actuarial local control rate of 82%, compared to 28% in lower doses. Treatment for CRC liver metastasis with single-fraction CIRT appeared to be safe up to 58 Gy (RBE) as long as the central hepatic portal region was avoided.

A systematic review of publications on charged particle therapy for hepatocellular carcinoma.

Charged particle therapy (proton beam therapy and carbon ion therapy) is a form of radiotherapy which has the unique characteristic of superior depth dose distribution, and has been used for the treatment of hepatocellular carcinoma (HCC) in a limited number of patients, especially in Japan. We undertook a systematic review to define the clinical utility of charged particle therapy for patients with HCC. We searched the MEDLINE database from 1983 to June 2016 to identify clinical studies on charged particle therapy for HCC. Primary outcomes of interest were local control, overall survival, and late radiation morbidities. A total of 13 cohorts from 11 papers were selected from an initial dataset of 78 papers. They included a randomized controlled trial comparing proton beam therapy with transarterial chemoembolization, 9 phase I or II trials and 2 retrospective studies. The reported actuarial local control rates ranged from 71.4-95% at 3 years, and the overall survival rates ranged from 25-42.3% at 5 years. Late severe radiation morbidities were uncommon, and a total of 18 patients with grade ≥3 late adverse events were reported among the 787 patients included in this analysis. Charged particle therapy for HCC was associated with good local control with limited probability of severe morbidities. The cost-effectiveness and the distinctive clinical advantages of charged particle therapies should be clarified in order to become a socially accepted treatment modality for HCC.

Combined intensity-modulated radiotherapy plus raster-scanned carbon ion boost for advanced adenoid cystic carcinoma of the head and neck results in superior locoregional control and overall survival.

BACKGROUND: Local control in patients with adenoid cystic carcinoma (ACC) of the head and neck remains a challenge because of the relative radioresistance of these tumors. This prospective carbon ion pilot project was designed to evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost (C12 therapy). The authors present the first analysis of long-term outcomes of raster-scanned C12 therapy compared with modern photon techniques. METHODS: Patients with inoperable or subtotally resected ACC received C12 therapy within the pilot project. Whenever C12 was not available, patients were offered IMRT or fractionated stereotactic radiotherapy (FSRT). Patients received either C12 therapy at a C12 dose of 3 Gray equivalents (GyE) per fraction up to 18 GyE followed by 54 Gray (Gy) of IMRT or IMRT up to a median total dose of 66 Gy. Toxicity was evaluated according to version 3 of the Common Toxicity Terminology for Adverse Events. Locoregional control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed using the Kaplan-Meier method. RESULTS: Fifty-eight patients received C12 therapy, and 37 received photons (IMRT or FSRT). The median follow-up was 74 months in the C12 group and 63 months in the photon group. Overall, 90% of patients in the C12 group and 94% of those in the photon group had T4 tumors; and the most common disease sites were paranasal sinus, parotid with skull base invasion, and nasopharynx. LC, PFS, and OS at 5 years were significantly higher in the C12 group (59.6%, 48.4%, 76.5%, respectively) compared with the photon group (39.9%, 27%, and 58.7%, respectively). There was no significant difference between patients who had subtotally resected and inoperable ACC. CONCLUSIONS: C12 therapy resulted in superior LC, PFS, and OS without a significant difference between patients with inoperable and partially resected ACC. Extensive and morbid resections in patients with advanced ACC may need to be reconsidered. The most common site of locoregional recurrence remains in field, and further C12 dose escalation should be evaluated.

Unexpected radiation laryngeal necrosis after carbon ion therapy using conventional dose fractionation for laryngeal cancer.

Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy.

Could hyperthermia with proton therapy mimic carbon ion therapy? Exploring a thermo-radiobiological rationale.

Hyperthermia has been conventionally used in conjunction with photon beam irradiation. With a gradual increase in particle therapy facilities worldwide, this paper explores the physical, thermal and radiobiological implications of using a combination of hyperthermia with proton beam therapy. Hyperthermia is known to exhibit radiobiological features similar to those of high linear energy transfer radiation. Protons have many of the physical dose distribution properties of (12)C ion therapy. Thus, the thermo-radiobiological advantages of hyperthermia coupled with the physical dose distribution advantages of proton beams could possibly mimic (12)C ion therapy.

Preliminary study of low-pressure ionization chamber for online dose monitoring in FLASH carbon ion radiotherapy.

The FLASH effect of carbon ion therapy has recently attracted significant attention from the scientific community. However, the radiobiological mechanism of the effect and the exact therapeutic conditions are still under investigation. Therefore, the dosimetry accuracy is critical for testing hypotheses about the effect and quantifying FLASH Radiotherapy. In this paper, the FLASH ionization chamber at low-pressure was designed, and its dose rate dependence was verified with the Faraday cup. In addition, the dose response was tested under the air pressure of the ionization chamber of 10 mbar, 80 mbar and 845 mbar, respectively. The results showed that when the pressure was 10 mbar, the dose linearity was verified and calibrated at the dose rate of ∼50 Gy s-1, and the residuals were less than 2%. In conclusion, the FLASH ionization chamber is a promising instrument for online dose monitoring.

Technical Note: Improving the workflow in a carbon ion therapy center with custom software for enhanced patient care.

Carbon-ion radiation therapy (CIRT) is an up-and-coming modality for cancer treatment. Implementation of CIRT requires collaboration among specialists like radiation oncologists, medical physicists, and other healthcare professionals. Effective communication among team members is necessary for the success of CIRT. However, the current workflows involving data management, treatment planning, scheduling, and quality assurance (QA) can be susceptible to errors, leading to delays and decreased efficiency. With the aim of addressing these challenges, a team of medical physicists developed an in-house workflow management software using FileMaker Pro. This tool has streamlined the workflow and improved the efficiency and quality of patient care.

Evaluating an analytical prediction algorithm of positron emitter distributions in patient data for PET monitoring of carbon ion therapy: A simulation study.

In vivo treatment monitoring in ion therapy is one of the key issues for improving the treatment quality assurance procedures. Range verification is one of the most relevant and yet complex task used for in vivo treatment monitoring. In carbon ion therapy, positron emission tomography is the most widely used method. This technique exploits the ß+-activity of positron emitters created by nuclear interactions between the incoming beam and the irradiated tissue. Currently, high computational efforts and time-consuming Monte Carlo simulation platforms are typically used to predict positron emitter distributions. In order to avoid time-consuming simulations, an extended filtering approach was suggested to analytically predict positron emitter profiles from depth dose distributions in carbon ion therapy. The purpose of this work is to investigate such an analytical prediction model in patient anatomies of varying complexity, highlighting its potential and the need of further improvements, especially in highly heterogeneous anatomies where many air cavities are present in the beam path. The accuracy of range verification showed a mean relative error of ∼3% and a deviation between the simulation and the prediction below 2mm for the three patient cases analysed: a brain case and two head and neck cases. Additional investigations demonstrated the region of applicability of the method for cases of patient data. The analytical method enables range verification in carbon ion therapy by replacing computing-intensive Monte Carlo simulations and thus minimize the PET monitoring burden on the clinical workflow.

Chronic Encapsulated Intracerebral Hematoma after Carbon Ion Therapy for Chordoma Mimicking Malignant Glioma: A Case Report.

Chronic encapsulated intracerebral hematoma is a rare type of intracerebral hemorrhage. Reportedly, it is associated with vascular malformations, including arteriovenous malformations, cavernous hemangiomas, microaneurysms, and venous malformations. Recently, an association between chronic encapsulated intracerebral hematoma and stereotactic radiosurgery for arteriovenous malformations has been reported. In general, as the hematoma enlarges, symptoms progress slowly. In this report, we present a case of a 50-year-old woman who had undergone clivus chordoma resection and carbon ion therapy for the clivus respectively 27 and 20 years before developing chronic encapsulated intracerebral hematoma with rapidly progressing disturbance of consciousness. She was referred to our hospital because of difficulty walking due to left hemiparesis. Head computed tomography and magnetic resonance imaging showed a cystic lesion in the right temporal lobe with perifocal edema. On the second day of hospitalization, the patient's consciousness worsened. We suspected a malignant glioma and performed an emergency craniotomy; however, the pathological diagnosis was chronic encapsulated intracerebral hematoma. After the rehabilitation therapy, the patient became ambulatory and was discharged. To the date of reporting, the patient remained recurrence-free. Chronic encapsulated intracerebral hematoma may be due to invasive craniotomy or carbon ion therapy. It usually progresses slowly; however, in some cases, such as this one, it may cause rapid deterioration of consciousness.

Toxicity profile of patients treated with proton and carbon-ion therapy for primary nasopharyngeal carcinoma: A systematic review and meta-analysis.

BACKGROUND: Proton and carbon-ion therapy may spare normal tissues in regions with many critical structures surrounding the target volume. As toxicity outcome data are emerging, we aimed to synthesize the published data for the toxicity outcomes of proton or carbon-ion therapy (together known as particle beam therapy [PBT]) for primary nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify original studies reporting toxicity outcomes following PBT of primary NPC. Quality assessment was performed using NIH's Quality Assessment Tool. Reports were extracted for information on demographics, main results, and clinical and dose factors correlates. Meta-analysis was performed using the random-effects model. RESULTS: Twelve studies were selected (six using mixed particle-photon beams, five performed comparisons to photon-based therapy). The pooled event rates for acute grade ≥2 toxicities mucositis, dermatitis, xerostomia weight loss are 46% (95% confidence interval [95% CI]-29%-64%, I2 = 87%), 47% (95% CI-28%-67%, I2 = 87%), 16% (95% CI-9%-29%, I2 = 76%), and 36% (95% CI-27%-47%, I2 = 45%), respectively. Only one late endpoint (xerostomia grade ≥2) has sufficient data for analysis with pooled event rate of 9% (95% CI-3%-29%, I2 = 77%), lower than intensity-modulated radiotherapy 27% (95% CI-10%-54%, I2 = 95%). For most endpoints with significant differences between the PBT and photon-based therapies, PBT resulted in better outcomes. In two studies where dose distribution was studied, doses to the organs at risk were independent risk factors for toxicities. CONCLUSION: PBT may reduce the risk of acute toxicities for patients treated for primary NPC, likely due to dose reduction to critical structures. The pooled event rate for toxicities derived in this study can be a guide for patient counseling.