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Purpose/objective To understand the role of relative biological effectiveness (RBE) and dose-averaged linear energy transfer (LETd) distributions in the treatment of sacral chordoma (SC) patients with carbon ion radiotherapy (CIRT). Material/methods Clinical plans of 50 SC patients consecutively treated before August 2018 with a local effect model-based optimization were recalculated with the modified microdosimetric kinetic RBE model (mMKM). Twenty-six patients were classified as progressive disease and the relapse volume was contoured on the corresponding follow-up diagnostic sequence. The remaining 24 patients populated the control group. Target prescription dose (DRBE|50%), near-to-minimum- (DRBE|95%) and near-to-maximum- (DRBE|2%) doses were compared between the two cohorts in both RBE systems. LETd distribution was evaluated for in-field relapsed cases with respect to the control group. Results Target DMKM|50% and DMKM|95% were respectively 10% and 18% lower than what we aimed at. Dosimetric evaluators showed no significant difference, in neither of the RBE frameworks, between relapsed and control sets. Half of the relapse volumes were located in a well-covered high dose region. On average, over these cases, median target LETd was significantly lower than the control cohort mean value (27 vs 30 keV/μm). Most notably, the volume receiving dose from high-LET particles (>50 keV/μm) lay substantially below recently reported data in the literature. Conclusion A combined multi model RBE- and LET-based optimization could play a key role in the enhancement of the therapeutic ratio of CIRT for large radioresistant tumors such as sacral chordomas.

BACKGROUND Radical cystectomy is considered the first choice for the treatment of muscle-invasive bladder cancer. However, for some patients who have lost the indications for surgery, external beam radiotherapy is a non-invasive and effective treatment. CASE SUMMARY A 76-year-old patient with bladder cancer who had serious comorbidities and could not tolerate surgery or chemotherapy came to the Wuwei Heavy Ion Center. He received carbon ion radiotherapy (CIRT) with a whole-bladder dose of 44 GyE and tumor boost of 20 GyE. When he finished CIRT, his bladder cancer-related hematuria completely disappeared, and computed tomography examination showed that the tumor had obviously decreased in size. At the 3-mo follow-up, the tumor disappeared, and there were no acute or late adverse events. CIRT was well tolerated in this patient. CONCLUSION CIRT may allow for avoiding resection and was well tolerated with curative outcomes.

Localized hepatocellular carcinoma (HCC) that is unresectable and non-transplantable can be treated by several liver-directed therapies. External beam radiation therapy (EBRT) is an increasingly accepted and widely utilized treatment modality in this setting. Accelerated charged particles such as proton beam therapy (PBT) and carbon ion radiation therapy (CIRT) offer technological advancements over conventional photon radiotherapy. In this review, we summarize the distinct advantages of CIRT use for HCC treatment, focusing on physical and biological attributes, and outline dosimetric and treatment planning caveats. Based on these considerations, we posit that HCC may be among the best indications for use of CIRT, as it allows for maximizing tumoricidal doses to the target volume while minimizing the dose to the organs at risk.

Carbon-ion radiotherapy (CIRT) is on the rise as a treatment choice for malignant tumor. Compared to conventional radiotherapy, particle beams have different physical and biological properties. Particle beam provides a low entry dose, deposits most of the energy at the endpoint of the flight path, and forms an asymptotic dose peak (the “Bragg peak”). Compared to protons, carbon with its larger mass decreases beam scattering, resulting in a sharper dose distribution border. We report a 50-year-old male who underwent CIRT without surgical resection on osteosarcoma of the mandible. After CIRT, the patient’s pain was gone, and the malignant mass remained stable with accompanying necrosis. Nine months later, however, magnetic resonance imaging demonstrated progression of the left mandibular osteosarcoma with pulmonary metastases. After multidisciplinary discussion, concurrent chemoradiotherapy was conducted. While necrotic bone segments came out of the mandible during subsequent periodic outpatient visits, the tumor itself was stable. Thirty months after his first visit and diagnosis, the patient is waiting for chemotherapy. Although CIRT is superior in treating radioresistant hypoxic disease, CIRT is in its infancy, so care must be taken for its indications and complications.

Purpose Carbon ion radiotherapy for prostate cancer was performed using two fine needle Gold Anchor (GA) markers for patient position verification in Osaka Heavy Ion Medical Accelerator in Kansai (Osaka HIMAK). The present study examined treatment plans for prostate cases using beam‐specific planning target volume (bsPTV) based on the effect of the markers on dose distribution and analysis of target movements. Materials and Methods Gafchromic EBT3 film was used to measure dose perturbations caused by markers. First, the relationships between the irradiated film density and absolute dose with different linear energy transfer distributions within a spread‐out Bragg peak (SOBP) were confirmed. Then, to derive the effect of markers, two types of markers, including GA, were placed at the proximal, center, and distal depths within the same SOBP, and dose distributions behind the markers were measured using the films. The amount of internal motion of prostate was derived from irradiation results and analyzed to determine the margins of the bsPTV. Results The linearity of the film densities against absolute doses was constant within the SOBP and the amount of dose perturbations caused by the markers was quantitatively estimated from the film densities. The dose perturbation close behind the markers was smallest (

Background Adenoid cystic carcinoma is a rare form of head and neck cancer with a slow, but aggressive growth pattern which remains a challenge for local tumor control. Based on phase II data, radiation treatment using partially high LET radiation results in a prolonged PFS and OS. There is a paucity of randomized clinical data examining the role of the use of high LET radiation only. Therefore, the purpose of this prospective clinical trial is to analyze local control rates in patients with node negative ACC treated with carbon ion radiotherapy alone compared to a combined modality approach. Methods This trial is conducted as a prospective, open-label, phase II, two-armed, investigator-initiated study comparing the local control rates in node negative ACCs of the head and neck treated either with sole carbon ion radiotherapy or a combination of carbon ions and photons. Secondary outcomes investigated are progression-free survival, overall survival, acute and late toxicity, and quality of life. A total of 314 patients will be randomly assigned to C12 treatment alone or bimodal treatment: Patients in the experimental group will receive a dose of 51 Gy (RBE) in 17 fractions and a boost of 15 Gy (RBE) in 5 fractions. Patients in the control group will receive 25 fractions photon IMRT 50Gy and a boost using 8 × 3 Gy (RBE) carbon ions. Local control will be assessed in regular follow up examinations until 5 years after the completion of treatment. Discussion The present trial aims to evaluate local control rates to compare sole carbon ion radiotherapy to bimodal radiotherapy with carbon ions and photons in patients with node negative ACCs of the head and neck region. Local control is selected as the primary endpoint due to its major clinical relevance because of slow but aggressive growth patterns. Trial registration The study was prospectively registered on 2nd January 2020: ClinicalTrials.gov, NCT04214366. “Adenoid Cystic Carcinoma and Carbon Ion Only Irradiation (ACCO)”. Study status Under recruitment, participant recruitment is not completed. Start of recruitment was January 2020. There are no results been published or submitted to any journal.

Macrovascular invasion (MVI), including portal vein tumor thrombosis (PVTT), is strongly associated with poor prognosis in patients with hepatocellular carcinoma (HCC). While recommended standard treatment for patients with advanced HCC is systemic therapy, various treatment approaches, including resection, transarterial chemoembolization, and radiation, have been empirically suggested to improve prognosis by eliminating or controlling MVI. Herein, we report our experience of a case with advanced HCC where MVI was controlled by carbon-ion radiotherapy (CIRT) while on systemic therapy, resulting in a prolonged survival. A female patient with HCC in her early 60s had multiple intrahepatic lesions (maximum 60 mm in diameter) with PVTT. The PVTT of this patient had reached the main trunk of the portal vein despite the use of lenvatinib. The other intrahepatic lesions of the patient, except PVTT, had been controlled by lenvatinib. Therefore, hoping to control PVTT, we attempted CIRT. The patient resumed lenvatinib therapy after the irradiation. During lenvatinib re-treatment, no evident progression of PVTT was observed in the patient.

There are no clinical reports of long‐term follow‐up after carbon‐ion radiotherapy (CIRT) using a dose of 51.6 Gy (relative biological effectiveness [RBE]) in 12 fractions for localized prostate cancer, or of a comparison of clinical outcomes between passive and scanning beam irradiation. A total of 256 patients with localized prostate cancer who received CIRT at a dose of 51.6 Gy (RBE) in 12 fractions using two different beam delivery techniques (passive [n = 45] and scanning [n = 211]), and who were followed for more than 1 year, were analyzed. The biochemical relapse‐free (bRF) rate was defined by the Phoenix definition, and the actuarial toxicity rates were evaluated using the Kaplan‐Meier method. Of the 256 patients, 41 (16.0%), 111 (43.4%), and 104 (40.6%) were classified as low, intermediate, and high risk, respectively, after a median follow‐up of 7.0 (range 1.1‐10.4) years. Androgen deprivation therapy was performed in 212 patients (82.8%). The 5‐year bRF rates of the low‐, intermediate‐, and high‐risk patients were 95.1%, 90.9%, and 91.1%, respectively. The 5‐year rates of grade 2 late gastrointestinal and genitourinary toxicities in all patients were 0.4% and 6.3%, respectively. No grade ≥3 toxicities were observed. There were no significant differences in the rates of bRF or grade 2 toxicities in patients who received passive irradiation versus scanning irradiation. Our long‐term follow‐up results showed that a CIRT regimen of 51.6 Gy (RBE) in 12 fractions for localized prostate cancer yielded a good therapeutic outcome and low toxicity rates irrespective of the beam delivery technique., A 51.6 Gy (relative biological effectiveness) carbon‐ion radiotherapy regimen in 12 fractions for localized prostate cancer with long‐term follow‐up yielded a good therapeutic outcome and low toxicity rates in both passive and scanning beam irradiation without significant difference.

Background: The National Institutes for Quantum and Radiological Science and Technology– National Institute of Radiological Sciences (QST–NIRS) has continuously investigated the undesired radiation exposure in ion beam radiotherapy mainly in carbon-ion radiotherapy (CIRT). This review introduces our investigations on the secondary neutron dose in CIRT with the broad and scanning beam methods. Materials and Methods: The neutron ambient dose equivalents in CIRT are evaluated based on rem meter (WENDI-II) measurements. The out-of-field organ doses assuming prostate cancer and pediatric brain tumor treatments are also evaluated through the Monte Carlo simulation. This evaluation of the out-of-field dose includes contributions from secondary neutrons and secondary charged particles. Results and Discussion: The measurements of the neutron ambient dose equivalents at a 90° angle to the beam axis in CIRT with the broad beam method show that the neutron dose per treatment dose in CIRT is lower than that in proton radiotherapy (PRT). For the scanning beam with the energy scanning technique, the neutron dose per treatment dose in CIRT is lower than that in PRT. Moreover, the out-of-field organ doses in CIRT decreased with distance to the target and are less than the lower bound in intensity-modulated radiotherapy (IMRT) shown in AAPM TG-158 (American Association of Physicists in Medicine Task Group). Conclusion: The evaluation of the out-of-field doses is important from the viewpoint of secondary cancer risk after radiotherapy. Secondary neutrons are the major source in CIRT, especially in the distant area from the target volume. However, the dose level in CIRT is similar or lower than that in PRT and IMRT, even if the contributions from all radiation species are included in the evaluation.

The study investigated the dosimetric impact of an iterative metal artifact reduction (iMAR) tool on carbon ion therapy for pelvic cancer patients with hip prostheses. An anthropomorphic pelvic phantom with unilateral and bilateral hip prostheses was used to simulate pelvic cancer patients with metal implants. The raw data obtained from phantom CT scanning were reconstructed with a regular filtered back projection (FBP) algorithm and then corrected with iMAR. The phantom without hip prosthesis was also scanned and used as a reference ground truth (GT). The CT images of three prostate and four sarcoma patients with unilateral hip prosthesis were also reconstructed by FBP and iMAR algorithm and compared. iMAR algorithm reduced the metal artifacts and the maximum WEPL deviation in phantom images from −19.1 to −0.4 mm. However, the CT numbers cannot be retrieved using iMAR for periprosthetic bone materials, eventually leading to a WEPL deviation of −3.6 mm. The use of iMAR improved large discrepancies in DVHs of PTVs and the gamma index between FBP and GT images but increased the difference in the bladder DVH for bilateral hip prostheses due to newly introduced artifacts. In the patient study, the discrepancies of dose distribution were small on iMAR images when compared with FBP images for most cases, except for two sarcoma cases where gamma analysis failed and dose coverage in 98% of the PTV maximally reduced due to large volume of dark metal artifacts. iMAR reduced the metal artifacts and improved dose distribution accuracy in carbon ion radiotherapy for pelvic cancer. However, the residual and newly introduced artifacts, especially with bilateral hip prostheses, may potentially increase WEPL inaccuracy and dose uncertainty. The use of iMAR has the potential to improve carbon ion treatment planning of pelvic cancer but should be used with caution.

Background Dose constraints are of paramount importance for the outcome of any radiotherapy treatment. In this article, we report dose-volume constraints as well as currently used fractionation schedules for carbon ion radiotherapy as applied in MedAustron (Wiener Neustadt, Austria). Materials and Methods For fractionation schedules, both German and Japanese regimes were used. From the clinical experience of National Institute of Radiological Sciences (Chiba, Japan) and Heidelberg Ion Therapy (Heidelberg, Germany; formerly GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany) and the work by colleagues in Centro Nazionale Adroterapia Oncologica (Pavia, Italy) recalculating the dose from the microdosimetric kinetic model to the local effect model, we have set the dose constraints for critical organs of the head and neck area. Where no clinical data was available, an educated guess was made, based on data available from photon and proton series. Results We report the constraints for the optic nerve and chiasm, brainstem, spinal cord, cochlea, brain parenchyma, salivary gland, eye and adnexa, and mandibular/maxillary bone; constraints are grouped based on a fractionation scheme (German versus Japanese) and the risk of toxicity (safe, low to middle, and middle to high). Conclusion We think validation of dose constraints should present a relevant part of the activity of any carbon ion radiotherapy facility, and we anticipate future multicentric, joint evaluations.

Background Daily anatomical deviations may distort the dose distribution in carbon ion radiotherapy (CIRT), which may cause treatment failure. Therefore, this study aimed to perform re-planning to maintain the dose coverage in patients with pancreatic cancer with passive scattering CIRT. Methods Eight patients with pancreatic cancer and 95 daily computed tomography (CT) sets were examined. Two types of adaptive plans based on new range compensators (RCs) (AP-1) and initial RCs (AP-2) were generated. In AP-2, each beam was optimized by manually adjusting the range shifter thickness and spread-out Bragg peak size to make dose reduction by Results Using TM and BM, mean ± standard deviations of daily CTV V95 (%) difference from the original plan was − 5.1 ± 6.2 and − 8.8 ± 8.8, respectively, but 1.2 ± 3.4 in AP-1 and − 0.5 ± 2.1 in AP-2 (P Conclusions The possible dose deterioration should be considered when performing the BM, even TM. Re-planning based on single beam optimization in passive scattering CIRT seems an effective and safe method of ensuring the treatment robustness in pancreatic cancer. Further study is necessary to spare healthy tissues, especially the duodenum.

The differentiation of non-small cell lung cancer (NSCLC) and radiation pneumonitis (RP) is critically essential for selecting optimal clinical therapeutic strategies to manage post carbon-ion radiotherapy (CIRT) in patients with NSCLC. The aim of this study was to assess the ability of 18F-FDG PET/CT metabolic parameters and its textural image features to differentiate NSCLC from RP after CIRT to develop a differential diagnosis of malignancy and benign lesion. We retrospectively analyzed 18F-FDG PET/CT image data from 32 patients with histopathologically proven NSCLC who were scheduled to undergo CIRT and 31 patients diagnosed with RP after CIRT. The SUV parameters, metabolic tumor volume (MTV), total lesion glycolysis (TLG) as well as fifty-six texture parameters derived from seven matrices were determined using PETSTAT image-analysis software. Data were statistically compared between NSCLC and RP using Wilcoxon rank-sum tests. Diagnostic accuracy was assessed using receiver operating characteristics (ROC) curves. Several texture parameters significantly differed between NSCLC and RP (p max, 0.64; GLRLM run percentage, 0.83 and NGTDM coarseness, 0.82. Diagnostic accuracy was improved using GLRLM run percentage or NGTDM coarseness compared with SUVmax (p 18F-FDG uptake yielded excellent outcomes for differentiating NSCLC from radiation pneumonitis after CIRT, which outperformed SUV-based evaluation. In particular, GLRLM run percentage and NGTDM coarseness of 18F-FDG PET/CT images would be appropriate parameters that can offer high diagnostic accuracy.

Charged-particle therapy (CPT) such as proton beam therapy (PBT) and carbon-ion radiotherapy (CIRT) exhibit substantial physical and biological advantages compared to conventional photon radiotherapy. As it can reduce the amount of radiation irradiated in the normal organ, CPT has been mainly applied to pediatric cancer and radioresistent tumors in the eloquent area. Although there is a possibility that more patients can benefit from it, high set-up cost and dearth of high level of clinical evidence hinders wide spread of CPT. This review aims to present recent clinical results of PBT and CIRT in selected diseases focusing on possible indications of CPT. We also discussed how clinical studies are conducted to increase the number of patients who can benefit from CPT considering the high cost of it.

The motivation for this study was to explore a new method to test the particle spatial distribution for a therapeutic carbon beam. CR-39 plastic nuclear track detectors were irradiated to a 276.5 MeV u−1 mono-energy carbon beam at the heavy ion facility in the Shanghai Proton and Heavy Ion Center. The spatial distribution of the primary carbon beam and secondary fragments in a water phantom were systematically analyzed both in the transverse direction (perpendicular to the projection direction of the primary beam) and at different depths in the longitudinal direction (along the projection direction of the primary beam) with measured tracks on the CR-39 detectors. Meanwhile, the theoretically spatial distribution and linear energy transfer (LET) spectra of the primary beam and secondary fragments were calculated using the Monte Carlo (MC) toolkit Geant4. The results showed that the CR-39 detectors are capable of providing high lateral resolution of carbon ion at different depths. In the range of the primary carbon beam, the beam width simulated with MC is in good agreement with that of experimental measurement. The track size registered in the CR-39 has a good correlation with the particle LET. These findings indicate that the CR-39 can be used for measuring both the particle flux and its spatial distribution of carbon ions.

Background Medulloblastomas with chromothripsis developing in children with Li-Fraumeni Syndrome (germline TP53 mutations) are highly aggressive brain tumors with dismal prognosis. Conventional photon radiotherapy and DNA-damaging chemotherapy are not successful for these patients and raise the risk of secondary malignancies. We hypothesized that the pronounced homologous recombination deficiency in these tumors might offer vulnerabilities that can be therapeutically utilized in combination with high linear energy transfer carbon ion radiotherapy. Methods We tested high-precision particle therapy with carbon ions and protons as well as topotecan with or without PARP inhibitor in orthotopic primary and matched relapsed patient-derived xenograft models. Tumor and normal tissue underwent longitudinal morphological MRI, cellular (markers of neurogenesis and DNA damage-repair), and molecular characterization (whole-genome sequencing). Results In the primary medulloblastoma model, carbon ions led to complete response in 79% of animals irrespective of PARP inhibitor within a follow-up period of 300 days postirradiation, as detected by MRI and histology. No sign of neurologic symptoms, impairment of neurogenesis or in-field carcinogenesis was detected in repair-deficient host mice. PARP inhibitors further enhanced the effect of proton irradiation. In the postradiotherapy relapsed tumor model, median survival was significantly increased after carbon ions (96 days) versus control (43 days, P < .0001). No major change in the clonal composition was detected in the relapsed model. Conclusion The high efficacy and favorable toxicity profile of carbon ions warrants further investigation in primary medulloblastomas with chromothripsis. Postradiotherapy relapsed medulloblastomas exhibit relative resistance compared to treatment-naïve tumors, calling for exploration of multimodal strategies.

Purpose We analyzed interfractional robustness of scanning carbon ion radiotherapy (CIRT) for prostate cancer based on the dose distribution using daily in‐room computed tomography (CT) images. Materials and Methods We analyzed 11 consecutive patients treated with scanning CIRT for localized prostate cancer in our hospital between December 2015 and January 2016. In‐room CT images were taken under treatment conditions in every treatment session. The dose distribution on each in‐room CT image was recalculated, while retaining the pencil beam arrangement of the initial treatment plan. Then, the dose–volume histogram (DVH) parameters including the percentage of the clinical target volume (CTV) with 95% and 90% of the prescribed dose area (V95% of CTV, V90% of CTV) and V80% of rectum were calculated. The acceptance criteria for the CTV and rectum were set at V95% of CTV ≥95%, V90% of CTV ≥98%, and V80% of rectum < 10 ml. Results V95% of CTV, V90% of CTV, and V80% of rectum for the reproduced plans were 98.8 ± 3.49%, 99.5 ± 2.15%, and 4.39 ± 3.96 ml, respectively. Acceptance of V95% of CTV, V90% of CTV, and V80% of rectum was obtained in 123 (94%), 125 (95%) and 117 sessions (89%), respectively. Acceptance of the mean dose of V95% of CTV, V90% of CTV, and V80% of rectum for each patient was obtained in 10 (91%), 10 (91%), and 11 patients (100%), respectively. Conclusions We demonstrated acceptable interfractional robustness based on the dose distribution in scanning CIRT for prostate cancer.

We propose a two-step method to converse human tissue materials from patient computed tomography (CT) images, which is required in dose reconstructions for a retrospective study of carbon-ion radiotherapy (CIRT) using Monte Carlo (MC) simulation. The first step was to assign the standard tissues of the International Commission on Radiological Protection reference phantoms according to the CT-number. The second step was to determine the mass density of each material based on the relationship between CT-number and stopping power ratio (Hounsfield unit [HU]-SPR) registered in treatment planning system (TPS). Direct implementation of the well-calibrated HU-SPR curve allows the reproduction of previous clinical treatments recorded in TPS without uncertainty due to a mismatch of the CT scanner or scanning conditions, whereas MC simulation with realistic human tissue materials can fulfill the out-of-field dose, which was missing in the record. To validate our proposed method, depth-dose distributions in the homogenous and heterogeneous phantoms irradiated by a 400 MeV/u carbon beam with an 8 cm spread-out Bragg peak (SOBP) were computed by the MC simulation in combination with the proposed methods and compared with those of TPS. Good agreement of the depth-dose distributions between the TPS and MC simulation (within a 1% discrepancy in range) was obtained for different materials. In contrast, fluence distributions of secondary particles revealed the necessity of MC simulation using realistic human tissue. The proposed material assignment method will be used for a retrospective study using previous clinical data of CIRT at the National Institute of Radiological Sciences (NIRS).

Purpose The robustness against setup and motion uncertainties of gated four-dimensional restricted robust optimization (4DRRO) was investigated for hypofractionated carbon ion radiotherapy (CIRT) of lung tumors. Methods CIRT plans of 9 patients were optimized using 4DRRO strategy with 3 mm setup errors, 3% density errors and 3 breathing phases related to the gate window. The prescription was 60 Gy(RBE) in 4 fractions. Standard spots (SS) were compared to big spots (BS). Plans were recalculated on multiple 4DCTs acquired within 3 weeks from treatment simulation and rigidly registered with planning images using bone matching. Warped dose distributions were generated using deformable image registration and accumulated on the planning 4DCTs. Target coverage (D98%, D95% and V95%) and dose to lung were evaluated in the recalculated and accumulated dose distributions. Results Comparable target coverage was obtained with both spot sizes (p = 0.53 for D95%). The mean lung dose increased of 0.6 Gy(RBE) with BS (p = 0.0078), still respecting the dose constraint of a 4-fraction stereotactic treatment for the risk of radiation pneumonitis. Statistically significant differences were found in the recalculated and accumulated D95% (p = 0.048 and p = 0.024), with BS showing to be more robust. Using BS, the average degradations of the D98%, D95% and V95% in the accumulated doses were −2.7%, −1.6% and −1.5%. Conclusions Gated 4DRRO was highly robust against setup and motion uncertainties. BS increased the dose to healthy tissues but were more robust than SS. The selected optimization settings guaranteed adequate target coverage during the simulated treatment course with acceptable risk of toxicity.

Our study was to investigate the value of pretreatment 18F-FDG uptake heterogeneity to predict the prognosis of patients with locally recurrent nasopharyngeal carcinoma (LRNPC) treated by carbon ion radiotherapy (CIRT). Twenty-nine LRNPC patients who underwent whole-body 18F-FDG PET/CT scanning before CIRT were enrolled. Heterogeneity index (HI)-based 18F-FDG uptake, and the PET/CT traditional parameters, including SUVmax, MTV, and TLG were assessed. Receiver operator characteristics (ROC) determined the best cutoff value, and local recurrence-free survival (LRFS) and progression-free survival (PFS) were evaluated by the Kaplan–Meier method and log-rank test. And the predictive ability was evaluated by the ROC curve. Cox analyses were performed on LRFS and PFS. In this study, univariate analysis showed that HI was a significant predictor of LRNPC treated by CIRT. HI could be used to predict LRFS and PFS. Patients with HI (≥ 0.81) had a significantly worse prognosis of LRFS (12.25 vs. NR, p = 0.008), and of PFS (10.58 vs. NR, p = 0.014). The AUC and its sensitivity and sensitivity and specificity were 0.75, 84.21% and 70.00% for LRFS and 0.82, 80.95% and 75.00% for PFS, respectively. Multivariate analysis showed that HI was an independent predictor for the LFRS of LRNPC with CIRT. 18F-FDG uptake heterogeneity may be useful for predicting the prognosis of patients with LRNPC treated by CIRT.

Ping Li,1– 3,* Chang Liu,4– 6,* Shuang Wu,2,3,7 Lin Deng,2,3,8 Guangyuan Zhang,2,3,8 Xin Cai,1– 3 Silong Hu,4– 6 Jingyi Cheng,2,3,6,9 Xiaoping Xu,4– 6 Bin Wu,2,3,10 Xiaomao Guo,2,3,7 Yingjian Zhang,4– 6 Shen Fu,5,11 Qing Zhang1– 3 1Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Radiation Oncology, Shanghai, People’s Republic of China; 3Shanghai Engineering Research Center of Proton and Heavy ion Radiation Therapy, Shanghai, People’s Republic of China; 4Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 5Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People’s Republic of China; 6Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People’s Republic of China; 7Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, People’s Republic of China; 8Department of Radiology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China; 9Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, People’s Republic of China; 10Department of Radiology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, People’s Republic of China; 11Department of Radiation Oncology, Shanghai Concord Cancer Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing ZhangDepartment of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of ChinaTel +86 139 1737 4609Fax +86 2138296518Email qing.zhang@hotmail.comShen FuDepartment of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of ChinaEmail shen_fu@hotmail.comPurpose: The purpose of this study was to assess the potential of 99mTc-labeled PSMA-SPECT/CT and diffusion-weighted image (DWI) for predicting treatment response after carbon ion radiotherapy (CIRT) in prostate cancer.Patients and Methods: We prospectively registered 26 patients with localized prostate cancer treated with CIRT. All patients underwent 99mTc-labeled PSMA-SPECT/CT and multiparametric magnetic resonance imaging (MRI) before and after CIRT. The tumor/background ratio (TBR) and mean apparent diffusion coefficient (ADCmean) were measured on the tumor and the percentage changes before and after therapy (ΔTBR and ΔADCmean) were calculated. Patients were divided into two groups: good response and poor response according to clinical follow-up.Results: The median follow up time was 38.3months. The TBR was significantly decreased (p=0.001), while the ADCmean was significantly increased compared with the pretreatment value (p< 0.001). The ΔTBR and ΔADCmean were negatively correlated with each other (p = 0.002). On ROC curve analysis for predicting treatment response, the area under the ROC curve (AUC) of ΔTBR (0.867) for predicting good response was higher than that of ΔADCmean (0.819). The AUC of combined with ΔTBR and ΔADCmean (0.895) was higher than that of either ΔADCmean or ΔTBR alone. The combined use of ΔTBR and ΔADCmean showed 91.4% sensitivity and 95.2% specificity.Conclusion: Our preliminary data indicate that the changes of TBR and ADCmean maybe an early bio-marker for predicting prognosis after CIRT in localized prostate cancer patients. In addition, the ΔTBR seems to be a more powerful prognostic factor than ΔADCmean in prostate cancer treated with CIRT.Keywords: PSMA, DWI, prostate cancer, carbon ion radiotherapy

AIM The treatment of hepatocellular carcinoma in the caudate lobe (HCCCL) is technically challenging. We aimed to investigate the efficacy and toxicity of carbon ion radiotherapy (C-ion RT) for HCCCL. METHODS Patients with HCCCL treated with C-ion RT at our hospital between January 2011 and December 2018 were evaluated. The total dose was 52.8 or 60 Gy (relative biological effectiveness) in four or 12 fractions depending on the distance between the tumor and the gastrointestinal tract. The survival outcome, the presence or absence of recurrence (local recurrence, intrahepatic recurrence outside the irradiation field, or extrahepatic recurrence), and acute/late adverse events were evaluated. RESULTS Nine patients were included. The median tumor size was 3.4 cm, and the median follow-up duration was 18.3 months for all patients. No patient developed local recurrence during follow-up. Five patients subsequently developed intrahepatic recurrence outside the irradiation field and two had extrahepatic metastasis. Five patients died of hepatocellular carcinoma. No acute adverse events of grade ≥2 were observed. Two patients experienced grade 2 or 3 late adverse events, including obstructive jaundice, hepatic encephalopathy, ascites, and edema. CONCLUSION Carbon ion radiotherapy for HCCCL achieved excellent local control with acceptable adverse events and can thus be a curative treatment option for HCCCL.

Background This study evaluated carbon-ion radiotherapy (C-ion RT) for oral non-squamous cell carcinomas (non-SCC). Methods We retrospectively obtained data from 74 patients who underwent C-ion RT for oral malignancies between April 1997 and March 2016. The C-ion RT was administered in 16 fractions at a total dose of 57.6 or 64.0 Gy (relative biological effectiveness). Results Forty-three patients had salivary gland carcinomas, 29 patients had mucosal melanoma, and 2 patients had other types of pathologies. The tumors were classified as T1-T3 (24 cases), T4a (21 cases), or T4b (29 cases). The median follow-up was 49 months. The 5-year rates were 78.8% for local control, 36.2% for progression-free survival, and 58.3% for overall survival. Although 10 patients developed grade 3 osteoradionecrosis after C-ion RT, all patients maintained their mastication and deglutition functions after sequestrectomy and prosthesis placement. Conclusion C-ion RT was effective for oral non-SCC and had acceptable toxicities.

Background Following surgery for soft tissue sarcoma of the retroperitoneum, the predominant pattern of failure is local recurrence, which remains the main cause of death. Radiotherapy is utilized to reduce recurrence rates but the efficacy of this strategy has not been definitely established. As treatment tolerability is more favorable with preoperative radiotherapy, normofractionated neoadjuvant treatment is the current approach. The final results of the prospective, randomized STRASS (EORTC 62092) trial, which compared the efficacy of this combined treatment to that of surgery alone, are still awaited; preliminary results presented at the 2019 ASCO Annual Meeting indicated that combined treatment is associated with better local control in patients with liposarcoma (74.5% of the cohort, 11% benefit in abdominal progression free survival after 3 years, p = 0.049). Particles allow better sparing of surrounding tissues at risk, e.g., bowel epithelium, and carbon ions additionally offer biologic advantages and are preferred in slow growing tumors. Furthermore, hypofractionation allows for a significantly shorter treatment interval with a lower risk of progression during radiotherapy. Methods and design We present a prospective, randomized, monocentric phase II trial. Patients with resectable or marginally resectable, histologically confirmed soft tissue sarcoma of the retroperitoneum 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 safety and feasibility based on the proportion of grade 3–5 toxicity (CTCAE, version 5.0) in the first 12 months after surgery or discontinuation of treatment for any reason related to the treatment. Local control, local progression-free survival, disease-free survival, overall survival, and quality of life are the secondary endpoints of the study. Discussion The aim of this study is to confirm that hypofractionated, accelerated preoperative radiotherapy is safe and feasible. The rationale for the use of particle therapy is the potential for reduced toxicity. The data will lay the groundwork for a randomized phase III trial comparing hypofractionated proton and carbon ion irradiation with regard to local control. Trial registration ClinicalTrials.gov NCT04219202. Retrospectively registered on January 6, 2020

BACKGROUND/AIM This study aimed to determine appropriate deformable image registration (DIR) algorithms for pancreatic cancer patients undergoing carbon ion radiotherapy (CIRT). PATIENTS AND METHODS The performance of three types of DIR algorithms, including intensity-based DIR (iDIR), contour-based DIR (cDIR), and hybrid DIR (hDIR) were evaluated using seventy-one CT images from eight pancreatic cancer patients. Both the geometry of the CTV and subsequent dose warping discrepancies were evaluated using the dice similarity coefficient (DSC) and the difference in V95. RESULTS cDIR and hDIR had superior performance than iDIR in both DSC and V95 (p

Salvage radical prostatectomy is a therapeutic option for the biochemical recurrence of prostate cancer after radiotherapy. However, only one case report of salvage radical prostatectomy after carbon ion radiotherapy has been reported. We report a case of salvage robot-assisted radical prostatectomy for local recurrence of prostate cancer after carbon ion radiotherapy with surgical video. Owing to adhesion and degeneration after radiotherapy, difficulties in surgery and post-operative complications have been anticipated. However, surgery was feasible without severe peri- and post-operative complications. Salvage robot-assisted radical prostatectomy after carbon ion radiotherapy may be a reasonable therapeutic option. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-020-00464-w.

Background and purpose Usefulness of carbon ion radiotherapy (CIRT) for sacral chordoma has been reported from single institutions. We conducted a retrospective nationwide multicentre study to evaluate the clinical outcomes of CIRT for sacral chordoma in Japan. Materials and methods A total of 219 patients who underwent CIRT for sacral chordoma at institutions across Japan between December 2003 and July 2014 were included in this study. Results Median patient age was 67 years (range, 26–87 years). Most patients had no history of surgical resection (96%). The most frequent planning target volume (PTV) range was 100–500 mL (65%). The most frequently used dose-fractionation was 67.2 Gy (relative biological effectiveness) in 16 fractions (65%). The median follow-up was 56 months (range, 7–132 months). The 5-year overall survival (OS), progression-free survival, and local control rates were 84%, 48%, and 72%, respectively. Frequent sites of out-of-field recurrence included bone (9%) and lung (9%) metastases. The Cox proportional hazards model revealed that both younger age (P = 0.004) and smaller PTV (P = 0.001) were associated with significantly better OS. Acute toxicities of ≥Grade 3 occurred in eight patients (4%). Late toxicities of ≥Grade 3 occurred in 13 patients (6%): skin disorders in six patients (3%), pain in three (1%), myositis in three (1%), etc. Conclusion Our retrospective nationwide multicentre study showed that CIRT for sacral chordoma was effective and safe, and replicated the previously reported data from a representative CIRT institution in Japan demonstrating high local control and low toxicity rates.

Highlights • Carbon-ion re-irradiation for pancreatic cancer; feasibility and efficacy. • Adjuvant chemotherapy improve local control of re-irradiation using carbon ions. • Carbon-ion radiotherapy for recurrent pancreatic cancer; reasonable option., Background and purpose Patients who receive carbon-ion radiotherapy (C-ion RT) for primary pancreatic cancer may experience locoregional recurrence; however, the treatment options for such patients are limited. We aimed to investigate the feasibility and efficacy of carbon-ion re-irradiation for patients with pancreatic cancer who experienced recurrence after initial C-ion RT. Materials and methods Twenty-one patients with recurrent pancreatic cancer who underwent repeat C-ion RT between December 2010 and November 2016 at our institute were retrospectively evaluated. The sites of post-initial C-ion RT failure were in-field central in 16 patients (76.2%) and marginal in 5 (23.8%). The median doses of initial and repeat C-ion RT were both 52.8 Gy (relative biological effectiveness [RBE]). Thirteen patients (61.9%) received concurrent chemotherapy with re-irradiation, while 11 (52.4%) received adjuvant chemotherapy. Results The median follow-up period after re-irradiation was 11 months. The 1-year local control, progression-free survival, and overall survival rates were 53.5%, 24.5%, and 48.7%, respectively. Toxicity data was obtained from the patients’ charts. Only 1 patient (4.8%) developed grade 3 acute toxicities and none developed grade ≥3 late toxicities. Univariate analysis indicated that patients who received adjuvant chemotherapy had significantly improved local control rates compared with those who did not; the 1-year local control rates were 80.0% and 0.0%, respectively (P = 0.0469). Conclusion Repeating C-ion RT may be a reasonable option with tolerable toxicity for patients with recurrent pancreatic cancers. Adjuvant chemotherapy appears to improve the local control rate. This is the first study to examine re-irradiation using C-ion for recurrent pancreatic cancer after initial C-ion RT.