[Objective] The aim of this study was to compare the efficacy of particle beam therapy (PT) with photon radiotherapy (RT) for treatment of skull base chordoma. [Methods] A systematic review was conducted for skull base chordoma treated with PT or photon RT reported from 1990 to 2022. Data were extracted for overall survival (OS) and progression-free survival (PFS), late adverse events, age, gender, gross total resection (GTR) rates, tumor volume, total irradiation dose, and treatment modality. Random-effects meta-regression analysis with the treatment modality as an explanatory variable was performed for each outcome to compare the modalities. [Results] A meta-analysis of 30 selected articles found 3- and 5-year OS rates for PT vs. photon RT or combined photon RT/proton beam therapy (PBT) of 90.8% (95% CI: 87.4-93.3%) vs. 89.5% (95% CI: 83.0-93.6%), p = 0.6543; 80.0% (95% CI: 75.7-83.6%) vs. 89.5% (95% CI: 83.0-93.6%), p = 0.6787. The 5-year PFS rates for PT vs. photon RT or photon RT/PBT were 67.8% (95% CI: 56.5-76.7%) vs. 40.2% (95% CI: 31.6-48.7%), p = 0.0004. A random-effects model revealed that the treatment modality (PT vs. photon RT or photon RT/PBT) was not a significant factor for 3-year OS (p = 0.42) and 5-year OS (p = 0.11), but was a significant factor for 5-year PFS (p < 0.0001). The rates of brain necrosis were 8-50% after PT and 0-4% after photon RT or photon RT/PBT. [Conclusion] This study shows that PT results in higher PFS compared to photon RT for skull base chordoma, but that there is a tendency for a higher incidence of brain necrosis with PT. Publication and analysis of further studies is needed to validate these findings.

BACKGROUND: Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan.
METHODS: A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients).
RESULTS: The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis.
CONCLUSIONS: The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group.

Background/Objectives: Particle beam therapy (PBT) was approved in April 2018 for head and neck malignancies and has since been introduced as a radical therapy for parotid malignancies. However, its prevalence and effectiveness in relation to surgical treatment have not been investigated. Methods: In this study, we evaluated 36 patients with parotid malignancy who underwent surgery (n = 26) or PBT (n = 10) and then analyzed the annual changes in the number of patients, survival rates, and clinical factors affecting prognosis. Results: Of the ten patients who opted for PBT, two and eight patients underwent PBT before and after 2018, respectively. There was a significant difference between these two groups of patients (p = 0.04). Of the ten patients who underwent PBT, five patients were recurrent cases; meanwhile, all twenty-six patients who underwent surgery were receiving initial treatment. Only one patient in each group had local recurrence after the treatment. Conclusions: The use of PBT as a radical therapy for parotid malignancies has been increasing since 2018, and patients with recurrent tumors tended to choose PBT. The outcome of the patients who underwent PBT did not seem to be inferior compared with those of the patients who underwent surgery. The histopathological type was a crucial issue in the outcomes of patients who underwent radical therapy for parotid malignancies.

BACKGROUND: Australia\'s first proton beam therapy (PBT) centre will house a fixed-beam room and two gantry rooms. As the only PBT facility in Australia for at least the short term, there is a need to efficiently allocate treatment appointments between the gantry and fixed-beam rooms. This planning study assesses the dosimetric differences between fixed-beam and gantry-based treatment plans for base of skull chordoma, one of the core indications likely to be referred for PBT in Australia.
METHODS: Retrospective gantry-based and fixed-beam treatment plans were generated for five patients with base of skull chordoma. Fixed-beam plans were generated with a conventional horizontal patient positioning system. Robust intensity modulated proton therapy (IMPT) optimisation and evaluation techniques were used for both delivery systems. Plans were designed to maximise target coverage while adhering to maximum dose constraints to neighbouring critical organs at risk.
RESULTS: Robust target coverage and integral dose were found to be approximately equivalent for the gantry-based and fixed-beam plans. Doses to specific organs at risk could be reduced with the gantry-based geometry; however, the gantry-based plans did not exhibit a general decrease in doses to organs at risk.
CONCLUSIONS: A fixed-beam treatment plan was found to be non-inferior to a gantry-based treatment plan for all base of skull patients included in the current study.

OBJECTIVE: Compared with radiation therapy using photon beams, particle therapies, especially those using carbons, show a high relative biological effectiveness and low oxygen enhancement ratio. Using cells cultured under normoxic conditions, our group reported a greater suppressive effect on cell growth by carbon beams than X-rays, and the subsequent therapeutic effect can be predicted by the cell uptake amount of 3\'-deoxy-3\'-[18F]fluorothymidine (18F-FLT) the day after treatment. On the other hand, a hypoxic environment forms locally around solid tumors, influencing the therapeutic effect of radiotherapy. In this study, the influence of tumor hypoxia on particle therapies and the ability to predict the therapeutic effect using 18F-FLT were evaluated.
METHODS: Using a murine colon carcinoma cell line (colon 26) cultured under hypoxic conditions (1.0% O2 and 5.0% CO2), the suppressive effect on cell growth by X-ray, proton, and carbon irradiation was evaluated. In addition, the correlation between decreased 18F-FLT uptake after irradiation and subsequent suppression of cell proliferation was investigated.
RESULTS: Tumor cell growth was suppressed most efficiently by carbon-beam irradiation. 18F-FLT uptake temporarily increased the day after irradiation, especially in the low-dose irradiation groups, but then decreased from 50 h after irradiation, which is well correlated with the subsequent suppression on tumor cell growth.
CONCLUSIONS: Carbon beam treatment shows a strong therapeutic effect against cells under hypoxia. Unlike normoxic tumors, it is desirable to perform 18F-FLT positron emission tomography 2-3 days after irradiation for early prediction of the treatment effect.

OBJECTIVE: To determine the interaction of gemcitabine in chemoradiotherapy with heavy carbon ions in vitro in a mucoepidermoid carcinoma (MEC) cell line.
METHODS: The human lymphatic MEC metastasis cell line NCI-H292 was used. The cells were treated with photons, carbon ions, and gemcitabine. Survival fractions (SF), apoptosis, and cell cycle progression were analyzed. A paired two-sided t-test was used. Significance was defined as p<0.05.
RESULTS: Cell proliferation assays showed a significant reduction in SF for combined photon chemoradiation versus photons only. The linear-quadratic fits of combined therapy with carbon ion dose of 0 to 2.5 Gy led to reductions of mean 15% in SF. The LD50 (lethal radiation dose required to reduce cell survival by 50%) for carbon ions only was 0.7 Gy and for carbon ions with gemcitabine 0.6 Gy. The LD50 for photons (with gemcitabine) was 2.8 Gy (2.0 Gy) and for carbon ions (with gemcitabine) 0.7 Gy (0.6 Gy), resulting in a relative biological effectiveness at 10% cell survival (RBE10) of 3.0 (2.7). Carbon ions and photons reduced S phase and increased G2/M phase cell distribution. Isolated treatment with gemcitabine as well as combination with photons led to prolonged S phase transit, whereas combined treatment with carbon ions led to early accumulation in G2/M phase. A significant increase in the sub-G1 population as a hint of relevant number of apoptotic cells was not observed.
CONCLUSIONS: Gemcitabine showed radiosensitizing effects in combination with photons. The combination of gemcitabine and carbon ions had independent additive effects. Carbon ions only had a RBE10 of 3.0, compared to photons only. The combination of gemcitabine, photon, and carbon ions in patients with MEC seems promising and warrants further investigation.

We sought to accelerate 2D/3D image registration computation time using image synthesis with a deep neural network (DNN) to generate digitally reconstructed radiographic (DRR) images from X-ray flat panel detector (FPD) images. And we explored the feasibility of using our DNN in the patient setup verification application. Images of the prostate and of the head and neck (H&N) regions were acquired by two oblique X-ray fluoroscopic units and the treatment planning CT. DNN was designed to generate DRR images from the FPD image data. We evaluated the quality of the synthesized DRR images to compare the ground-truth DRR images using the peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM). Image registration accuracy and computation time were evaluated by comparing the 2D-3D image registration algorithm using DRR and FPD image data with DRR and synthesized DRR images. Mean PSNR values were 23.4 ± 3.7 dB and 24.1 ± 3.9 dB for the pelvic and H&N regions, respectively. Mean SSIM values for both cases were also similar (= 0.90). Image registration accuracy was degraded by a mean of 0.43 mm and 0.30°, it was clinically acceptable. Computation time was accelerated by a factor of 0.69. Our DNN successfully generated DRR images from FPD image data, and improved 2D-3D image registration computation time up to 37% in average.

We developed a deep neural network (DNN) to generate X-ray flat panel detector (FPD) images from digitally reconstructed radiographic (DRR) images. FPD and treatment planning CT images were acquired from patients with prostate and head and neck (H&N) malignancies. The DNN parameters were optimized for FPD image synthesis. The synthetic FPD images\' features were evaluated to compare to the corresponding ground-truth FPD images using mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM). The image quality of the synthetic FPD image was also compared with that of the DRR image to understand the performance of our DNN. For the prostate cases, the MAE of the synthetic FPD image was improved (= 0.12 ± 0.02) from that of the input DRR image (= 0.35 ± 0.08). The synthetic FPD image showed higher PSNRs (= 16.81 ± 1.54 dB) than those of the DRR image (= 8.74 ± 1.56 dB), while SSIMs for both images (= 0.69) were almost the same. All metrics for the synthetic FPD images of the H&N cases were improved (MAE 0.08 ± 0.03, PSNR 19.40 ± 2.83 dB, and SSIM 0.80 ± 0.04) compared to those for the DRR image (MAE 0.48 ± 0.11, PSNR 5.74 ± 1.63 dB, and SSIM 0.52 ± 0.09). Our DNN successfully generated FPD images from DRR images. This technique would be useful to increase throughput when images from two different modalities are compared by visual inspection.

This study presents the first data of a Japanese nationwide multi-institutional cohort and compares them with the findings of systematic literature reviews on radiation therapies and inoperable stage III non-small cell lung cancer (NSCLC) conducted by the Lung Cancer Working Group in the Particle Beam Therapy (PBT) Committee and Subcommittee at Japanese Society for Radiation Oncology. The Lung Cancer Working Group extracted eight reports and compared their data with those of the PBT registry from May 2016 to June 2018. All the analyzed 75 patients aged ≤80 years underwent proton therapy (PT) with concurrent chemotherapy for inoperable stage III NSCLC. The median follow-up period of the surviving patients was 39.5 (range, 1.6-55.6) months. The 2- and 3-year overall survival (OS) and progression-free survival rates were 73.6%/64.7% and 28.9%/25.1%, respectively. During the follow-up period, six patients (8.0%) had adverse events of Grade ≥ 3, excluding abnormal laboratory values. These included esophagitis in four patients, dermatitis in one and pneumonitis in one. Adverse events of Grade ≥ 4 were not observed. The results of these PBT registry data in patients with inoperable stage III NSCLC suggest that the OS rate was at least equivalent to that of radiation therapy using X-rays and that the incidence of severe radiation pneumonitis was low. PT may be an effective treatment to reduce toxicities of healthy tissues, including the lungs and heart, in patients with inoperable stage III NSCLC.

The aim of this study was to investigate the efficacy and safety of particle beam therapy (PBT) with proton or carbon ion beam for pelvic recurrence of colorectal cancer (PRCC) by comparing the clinical outcomes of a dataset of prospectively enrolled patients for PBT with those from the literature, which were collected by a systematic review of external X-ray radiotherapy (XRT) and PBT. Patients with PRCC treated at 14 domestic facilities between May 2016 and June 2019 and entered the database for prospective observational follow-up were analyzed. The registry data analyzed included 159 PRCC patients treated with PBT of whom 126 (79%) were treated with carbon ion radiation therapy (CIRT). The 3-year overall survival and local control rate were 81.8 and 76.4%, respectively. Among these PRCC patients, 5.7% had Grade 3 or higher toxicity. Systematic search of PubMed and Cochrane databases published from January 2000 to September 2020 resulted in 409 abstracts for the primary selection. Twelve studies fulfilled the inclusion criteria. With one additional publication, 13 studies were selected for qualitative analysis, including 9 on XRT and 4 on PBT. There were nine XRT studies, which included six on 3D conformal radiotherapy and three on stereotactic body radiation therapy, and four PBT studies included three on CIRT and one on proton therapy. A pilot meta-analysis using literatures with median survival time extractable over a 20-month observation period suggested that PBT, especially CIRT, may be a promising treatment option for PRCC not amenable to curative resection.