2,125 results on '"Heavy Ion Radiotherapy"'
Search Results
2. Revolutionizing cancer treatment in India: Evaluating the unmet need, economics, and a roadmap for project implementation of particle therapy.
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Gupta, Anil, Subramani, V., Kumar, Rishabh, Kareem, Rafi, Vishwanathan, Bhaskar, and Sharma, Daya Nand
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CANCER treatment , *CHILD patients , *OPERATING costs , *HIGH-income countries , *PROTON therapy - Abstract
Introduction: This study aims to quantitatively assess eligible patients and project the demand for particle therapy facilities in India from 2020 to 2040. In addition, an economic analysis evaluates the financial feasibility of implementing this technology. The study also examines the prospective benefits and challenges of adopting this technology in India. Methodology: Cancer incidence and projected trends were analyzed for pediatric patients using the Global Childhood Cancer microsimulation model and adult patients using the Globocan data. Economic cost evaluation is performed for large‐scale combined particle (carbon and proton‐three room fixed‐beam), large‐scale proton (one gantry and two fixed‐beam), and small‐scale proton (one gantry) facility. Results: By 2040, the estimated number of eligible patients for particle therapy is projected to reach 161,000, including approximately 14,000 pediatric cases. The demand for particle therapy facilities is projected to rise from 81 to 97 in 2020 to 121 to 146 by 2040. The capital expenditure is estimated to be only 3.7 times that of a standard photon linear accelerator over a 30‐year period. Notably, the treatment cost can be reduced to USD 400 to 800 per fraction, substantially lower than that in high‐income countries (USD 1000 to 3000 per fraction). Conclusion: This study indicates that, in the Indian scenario, all particle therapy models are cost‐beneficial and feasible, with large‐scale proton therapy being the most suitable. Despite challenges such as limited resources, space, a skilled workforce, referral systems, and patient affordability, it offers substantial benefits. These include the potential to treat many patients and convenient construction and operational costs. An iterative phased implementation strategy can effectively overcome these challenges, paving the way for the successful adoption of particle therapy in India. Plain Language Summary: In India, the number of eligible patients benefiting from high‐precision particle therapy technology is projected to rise till 2040. Despite high upfront costs, our study finds the long‐term feasibility of all particle therapy models, potentially offering a substantial reduction in treatment cost compared to high‐income countries. Despite challenges, India can succeed with an iterative phased approach. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Macro- and Micro-scale Dose Simulation of Heavy Ion Relative Biological Effectiveness
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HU Ziyi1,2, QIU Rui1,2, CHEN Yizheng4, HU Ankang1,2, WU Zhen1,3, ZHANG Hui1,2, LI Junli1
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heavy ion radiotherapy ,rbe ,multi-scale dosimetry ,multi-scale monte carlo ,Nuclear engineering. Atomic power ,TK9001-9401 ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Heavy ion therapy is an important cancer treatment. Accurate evaluation of the biophysical effects of heavy ions is of great significance to improve the refinement level of particle radiotherapy. An aim of this study is to calculate multi-scale relative biological effectiveness (RBE) of heavy ion. Based on multi-scale dosimetry and Monte Carto dose simulation, the RBE of carbon ions were calculated at the macro- and micro-scales, and the results were compared and analyzed to evaluate the biological effects of carbon ions comprehensively. In this study, different dose-effect models of carbon ions were used at the two scales: LQ model was used at macro-scale and microdosimetric kinetics model (MKM) was used at the micro-scale. The Monte Carlo simulation used a water phantom to calculate the macro-scale carbon ion RBE by counting the dose distribution and linear energy transfer (LET), and the information of the particles passing through the voxels was recorded as a secondary source. Micro-dose simulation was carried out with the secondary source to calculate the micro-scale carbon ion RBE. The results show that the RBE calculated at different scales in the plateau region differs by 16%, and the RBE at the Bragg peak differs by 25%. The results of this study presents a method for calculating heavy ion RBE at macro- and micro-scales under the same irradiation situation, and will provide references for the improvement and clinical application of different methods.
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- 2024
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4. Carbon‐ion radiotherapy for inoperable upper tract ureteral cancer.
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Mizukami, Tatsuji, Kawamura, Hidemasa, Kubo, Nobuteru, Sato, Hiro, Kawahara, Masahiro, Adachi, Akiko, Matsui, Hiroshi, Suzuki, Kazuhiro, Saitoh, Jun‐ichi, Nakano, Takashi, and Ohno, Tatsuya
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LYMPHATIC metastasis , *LIVER metastasis , *HEPATORENAL syndrome , *BLADDER cancer , *RADIOTHERAPY , *URETERIC obstruction , *KIDNEY physiology - Abstract
Aim: This study aimed to report initial results of hypofractionated carbon‐ion radiotherapy (C‐ion RT) for inoperable upper tract ureteral cancer. Methods: Retrospective chart review was performed for five consecutive patients with medically inoperable ureter cancer that was treated with radical C‐ion RT between December 2013 and December 2014. The median age of the patients was 80 years (range, 68–84 years). The reasons for inoperability were advanced age, post‐contralateral nephrectomy, alcoholic cirrhosis, both advanced age and contralateral renal function degeneracy, and pneumonia. The median size of tumor was 2.8 cm (range, 2.2–4.0 cm). Diagnostic imaging did not identify lymph node metastases or distant metastases in any case. All patients underwent C‐ion RT (52.8 Gy relative biological effectiveness; 12 fractions in 3 weeks). The clinical target volume encompassed the growth tumor volume with a 5‐mm margin bilaterally; there was a 40‐mm margin craniocaudally but the clinical target volume did not encompass the whole ureter. Results: Within a median follow‐up time of 32.9 months (range, 24–36 months), two patients died and three remained alive. Neither local recurrence nor regional lymph node metastases were observed. Secondary bladder tumor was observed in four patients, and one patient had a liver metastasis. Grade 1 hematuria was observed in two patients, and Grade 3 pyelonephritis was observed in one patient as acute toxicity. Ureteral obstruction was observed in two patients. Conclusion: C‐ion RT might be a useful treatment option for inoperable ureter cancer. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Toxicity profile of patients treated with proton and carbon‐ion therapy for primary nasopharyngeal carcinoma: A systematic review and meta‐analysis.
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Yahya, Noorazrul, Mohamad Salleh, Siti Athiyah, Mohd Nasir, Nurul Faiqah, and Abdul Manan, Hanani
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PROTON therapy , *NASOPHARYNX cancer , *PARTICLE beams , *INTENSITY modulated radiotherapy , *CONFIDENCE intervals - Abstract
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. [ABSTRACT FROM AUTHOR]
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- 2024
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6. 重离子相对生物效应的双尺度模拟方法比较研究.
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胡子仪, 邱睿, 陈宜正, 胡安康, 武祯, 张辉, and 李君利
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- 2024
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7. A Phase Ib Study of Durvalumab (MEDI4736) in Combination with Carbon-Ion Radiotherapy and Weekly Cisplatin for Patients with Locally Advanced Cervical Cancer (DECISION Study): The Early Safety and Efficacy Results.
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Okonogi, Noriyuki, Murata, Kazutoshi, Yamada, Shigeru, Habu, Yuji, Hori, Makoto, Kurokawa, Tomoya, Inaba, Yosuke, Fujiwara, Tadami, Fujii, Yasuhisa, Hanawa, Michiko, Kawasaki, Yohei, Hattori, Yoko, Suzuki, Kazuko, Tsuyuki, Kyoko, Wakatsuki, Masaru, Koto, Masashi, Hasegawa, Sumitaka, Ishikawa, Hitoshi, Hanaoka, Hideki, and Shozu, Makio
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CISPLATIN , *CERVICAL cancer , *RADIOTHERAPY , *TREATMENT effectiveness - Abstract
We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m2. Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study. [ABSTRACT FROM AUTHOR]
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- 2023
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8. A time-resolved clonogenic assay for improved cell survival and RBE measurements
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Robin A Koch, Marc Boucsein, Stephan Brons, Markus Alber, and Emanuel Bahn
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Radiobiology ,Dose-response relationship, radiation ,Relative biological effectiveness ,Heavy ion radiotherapy ,Time-lapse imaging ,Supervised machine learning ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Purpose: The in vitro clonogenic assay (IVCA) is the mainstay of quantitative radiobiology. Here, we investigate the benefit of a time-resolved IVCA version (trIVCA) to improve the quantification of clonogenic survival and relative biological effectiveness (RBE) by analyzing cell colony growth behavior. Materials & Methods: In the IVCA, clonogenicity classification of cell colonies is performed based on a fixed colony size threshold after incubation. In contrast, using trIVCA, we acquire time-lapse microscopy images during incubation and track the growth of each colony using neural-net-based image segmentation. Attributes of the resulting growth curves are then used as predictors for a decision tree classifier to determine clonogenicity of each colony. The method was applied to three cell lines, each irradiated with 250 kV X-rays in the range 0–8 Gy and carbon ions of high LET (100 keV/μm, dose-averaged) in the range 0–2 Gy. We compared the cell survival curves determined by trIVCA to those from the classical IVCA across different size thresholds and incubation times. Further, we investigated the impact of the assaying method on RBE determination. Results: Size distributions of abortive and clonogenic colonies overlap consistently, rendering perfect separation via size threshold unfeasible at any readout time. This effect is dose-dependent, systematically inflating the steepness and curvature of cell survival curves. Consequently, resulting cell survival estimates show variability between 3% and 105%. This uncertainty propagates into RBE calculation with variability between 8% and 25% at 2 Gy.Determining clonogenicity based on growth curves has an accuracy of 95% on average. Conclusion: The IVCA suffers from substantial uncertainty caused by the overlap of size distributions of delayed abortive and clonogenic colonies. This impairs precise quantification of cell survival and RBE. By considering colony growth over time, our method improves assaying clonogenicity.
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- 2023
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9. Radio-enhancement by gold nanoparticles and their impact on water radiolysis for x-ray, proton and carbon-ion beams.
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Rudek, Benedikt, McNamara, Aimee, Ramos-Méndez, Jose, Byrne, Hilary, Kuncic, Zdenka, and Schuemann, Jan
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Carbon Radioisotopes ,Gold ,Heavy Ion Radiotherapy ,Metal Nanoparticles ,Monte Carlo Method ,Protons ,Radiation-Sensitizing Agents ,Water ,X-Rays - Abstract
Gold nanoparticle (GNP) radio-enhancement is a promising technique to increase the dose deposition in a tumor while sparing neighboring healthy tissue. Previous experimental studies showed effects on cell survival and tumor control for keV x-rays but surprisingly also for MV-photons, proton and carbon-ion beams. In a systematic study, we use the Monte Carlo simulation tool TOPAS-nBio to model the GNP radio-enhancement within a cell as a function of GNP concentration, size and clustering for a wide range of energies for photons, protons and, for the first time, carbon-ions. Moreover, we include water radiolysis, which has been recognized as a major pathway of GNP mediated radio-enhancement. At a GNP concentration of 0.5% and a GNP diameter of 10 nm, the dose enhancement ratio was highest for 50 keV x-rays (1.36) and decreased in the orthovoltage (1.04 at 250 keV) and megavoltage range (1.01 at 1 MeV). The dose enhancement linearly increased with GNP concentration and decreased with GNP size and degree of clustering for all radiation modalities. While the highest physical dose enhancement at 5% concentrations was only 1.003 for 10 MeV protons and 1.004 for 100 MeV carbon-ions, we find the number of hydroxyl ([Formula: see text]) altered by 23% and 3% after 1 [Formula: see text]s at low, clinically-relevant concentrations. For the same concentration and proton-impact, the G-value is most sensitive to the nanoparticle size with 46 times more radical interactions at GNPs for 2 nm than for 50 nm GNP diameter within 1 [Formula: see text]s. Nanoparticle clustering was found to decrease the number of interactions at GNPs, e.g. for a cluster of 25 GNPs by a factor of 3.4. The changes in G-value correlate to the average distance between the chemical species and the GNPs. While the radiochemistry of GNP-loaded water has yet to be fully understood, this work offers a first relative quantification of radiolysis products for a broad parameter-set.
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- 2019
10. Simultaneous optimization of RBE-weighted dose and nanometric ionization distributions in treatment planning with carbon ions
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Burigo, Lucas N, Ramos-Méndez, José, Bangert, Mark, Schulte, Reinhard W, and Faddegon, Bruce
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Cancer ,Heavy Ion Radiotherapy ,Humans ,Neoplasms ,Organs at Risk ,Radiotherapy Dosage ,Radiotherapy Planning ,Computer-Assisted ,Relative Biological Effectiveness ,biological optimization ,treatment planning ,IMPT ,carbon ion ,nanodosimetry ,LET ,Other Physical Sciences ,Biomedical Engineering ,Clinical Sciences ,Nuclear Medicine & Medical Imaging - Abstract
Inverse treatment planning in intensity modulated particle therapy (IMPT) with scanned carbon-ion beams is currently based on the optimization of RBE-weighted dose to satisfy requirements of target coverage and limited toxicity to organs-at-risk (OARs) and healthy tissues. There are many feasible IMPT plans that meet these requirements, which allows the introduction of further criteria to narrow the selection of a biologically optimal treatment plan. We propose a novel treatment planning strategy based on the simultaneous optimization of RBE-weighted dose and nanometric ionization details (ID) as a new physical characteristic of the delivered plan beyond LET. In particular, we focus on the distribution of large ionization clusters (more than 3 ionizations) to enhance the biological effect across the target volume while minimizing biological effect in normal tissues. Carbon-ion treatment plans for different patient geometries and beam configurations generated with the simultaneous optimization strategy were compared against reference plans obtained with RBE-weighted dose optimization alone. Quality indicators, inhomogeneity index and planning volume histograms of RBE-weighted dose and large ionization clusters were used to evaluate the treatment plans. We show that with simultaneous optimization, ID distributions can be optimized in carbon-ion radiotherapy without compromising the RBE-weighted dose distributions. This strategy can potentially be used to account for optimization of endpoints closely related to radiation quality to achieve better tumor control and reduce risks of complications.
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- 2019
11. Clinical trials involving carbon‐ion radiation therapy and the path forward
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Lazar, Ann A, Schulte, Reinhard, Faddegon, Bruce, Blakely, Eleanor A, and Roach, Mack
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Trials and Supportive Activities ,Clinical Research ,Cancer ,Good Health and Well Being ,Clinical Trials ,Phase I as Topic ,Clinical Trials ,Phase II as Topic ,Heavy Ion Radiotherapy ,Humans ,Multicenter Studies as Topic ,Neoplasms ,Progression-Free Survival ,Randomized Controlled Trials as Topic ,Registries ,Sample Size ,Treatment Outcome ,carbon ,clinical trials ,heavy-ion radiotherapy ,ions ,particle therapy ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis ,Public health - Abstract
To describe the international landscape of clinical trials in carbon-ion radiotherapy (CIRT), the authors reviewed the current status of 63 ongoing clinical trials (median, 47 participants) involving CIRT identified from the US clinicaltrials.gov trial registry and the World Health Organization International Clinical Trials Platform Registry. The objectives were to evaluate the potential for these trials to define the role of this modality in the treatment of specific cancer types and identify the major challenges and opportunities to advance this technology. A significant body of literature suggested the potential for advantageous dose distributions and, in preclinical biologic studies, the enhanced effectiveness for CIRT compared with photons and protons. In addition, clinical evidence from phase I/II trials, although limited, indicated the potential for CIRT to improve cancer outcomes. However, current high-level phase III randomized clinical trial evidence does not exist. Although there has been an increase in the number of trials investigating CIRT since 2010, and the number of countries and sites offering CIRT is slowly growing, this progress has excluded other countries. Several recommendations are proposed to study this modality to accelerate progress in the field, including: 1) increasing the number of multinational randomized clinical trials, 2) leveraging the existing CIRT facilities to launch larger multinational trials directed at common cancers combined with high-level quality assurance; and 3) developing more compact and less expensive next-generation treatment systems integrated with radiobiologic research and preclinical testing.
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- 2018
12. Recoil Analysis for Heavy Ion Beams.
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Ekinci, Fatih, Bostanci, Erkan, Güzel, Mehmet Serdar, and Dagli, Ozlem
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RADIOTHERAPY ,ION beams ,ATOMS ,ATOMIC physics ,MONTE Carlo method - Published
- 2022
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13. Efficacy and Safety of 4 Fractions of Carbon-Ion Radiation Therapy for Hepatocellular Carcinoma: A Prospective Study
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Kei Shibuya, Hiroyuki Katoh, Yoshinori Koyama, Shintaro Shiba, Masahiko Okamoto, Shohei Okazaki, Kenichiro Araki, Satoru Kakizaki, Ken Shirabe, and Tatsuya Ohno
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hepatocellular carcinoma ,heavy ion radiotherapy ,carbon-ion radiotherapy ,prospective ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Prospective evidence supporting the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for hepatocellular carcinoma (HCC) remains lacking. This prospective study aimed to evaluate the safety and efficacy of hypofractionated C-ion RT in patients with HCC. Methods: The inclusion criteria were as follows: (1) pathologically or clinically diagnosed HCC; (2) measurable tumor and tumor size ≤10 cm; (3) absence of major vascular invasion; (4) no extrahepatic metastasis; (5) the alimentary tract was not adjacent to the target lesion (>1 cm); (6) not suitable for or refusal to undergo surgery or local ablative therapies; (7) an interval ≥4 weeks from previous therapy; (8) no other intrahepatic lesion or at least 2 years after the previous curative therapy; (9) performance status score, 0–2; and (10) Child-Pugh score, 5–9. The prescribed C-ion RT dose was 52.8 Gy (relative biological effectiveness [RBE]) or 60.0 Gy (RBE) in 4 fractions. Results: In total, 35 patients with HCC were enrolled between October 2010 and May 2016. The median follow-up durations in the survivor group (n = 23) and in the whole cohort were 55.1 and 49.0 months, respectively. The 2-, 3-, and 4-year overall survival rates were 82.8%, 76.7%, and 69.4%, respectively. The 2-, 3-, and 4-year local control (LC) rates were 92.6%, 76.5%, and 76.5%, respectively. The median time-to-progression was 25.6 months (95% confidence interval, 13.7–37.5 months). Grade 4 or 5 toxicities were not observed. Grade 3 acute and late toxicities were observed in 2 patients. There was no significant deterioration in serum albumin, bilirubin, prothrombin time-international normalized ratio, platelet count, or Child-Pugh score after C-ion RT. Conclusion: Four fractions of C-ion RT for HCC did not yield serious adverse events and showed promising LC, thus making it a safe and effective modality for this type of malignancy.
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- 2021
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14. A risk factor analysis for local recurrence of bone and soft tissue sarcoma treated with carbon ion radiotherapy: A retrospective cohort study at a single institution.
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Kohama, Isaku, Yanagawa, Takashi, Okamoto, Masahiko, Ohno, Tatsuya, and Chikuda, Hirotaka
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SARCOMA , *FACTOR analysis , *POSITRON emission tomography , *PROPORTIONAL hazards models , *OSTEOSARCOMA - Abstract
Aim: Carbon ion radiotherapy is well‐recognized as an excellent radiation modality that is suitable for treating unresectable bone and soft‐tissue sarcoma of the trunk, spine, and pelvis; however, further study is needed to improve the local control rate. The current study examined the risk factors of the local recurrence of sarcomas after carbon ion radiotherapy. Methods: Patients with inoperable bone and soft‐tissue sarcomas treated with carbon ion radiotherapy in our institute from 2010 to 2018 were retrospectively analyzed. Among them, 87 patients were eligible for this study. We divided the instances of local recurrence into two types, in‐field and out‐field recurrence, and evaluated the predictors for the risk of local recurrence such as the age at the treatment, sex, histopathological diagnosis, standard uptake value on fluorodeoxyglucose positron emission tomography, and the clinical target volume for each recurrence using a Cox proportional hazards model. Results: A multivariate analysis revealed that the tumors with a post‐treatment standard uptake value of more than 3.84 on positron emission tomography had a significantly high risk of in‐field recurrence (hazard ratio, 3.42; p =.03). Furthermore, postoperative lesions were a risk factor for out‐field recurrence (hazard ratio, 3.82; p <.01). Conclusion: The current study revealed that sarcomas maintaining a high glucose metabolic activity after carbon ion radiotherapy carried a risk of in‐field recurrence, and the most significant risk factor of out‐field recurrence was identified to be surgery before CIRT. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Charged particle radiotherapy for thyroid cancer. A systematic review.
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Ciccone LP, Franzetti J, Bonora M, Ronchi S, Camarda AM, Charalampopoulou A, Facoetti A, Bazani A, Magro G, Vischioni B, Locati LD, Licitra L, Sauerwein WAG, and Orlandi E
- Abstract
The role of external beam radiotherapy (EBRT) in thyroid cancer (TC) remains contentious due to limited data. Retrospective studies suggest adjuvant EBRT benefits high-risk differentiated thyroid cancer (DTC) and limited-stage anaplastic thyroid carcinoma (ATC), enhancing locoregional control and progression-free survival when combined with surgery and chemotherapy. Intensity-modulated radiotherapy (IMRT) and particle therapy (PT), including protons, carbon ions, and Boron Neutron Capture Therapy (BNCT), represent advances in TC treatment. Following PRISMA guidelines, we reviewed 471 studies from January 2002 to January 2024, selecting 14 articles (10 preclinical, 4 clinical). Preclinical research focused on BNCT in ATC mouse models, showing promising local control rates. Clinical studies explored proton, neutron, or photon radiotherapy, reporting favorable outcomes and manageable toxicity. While PT shows promise supported by biological rationale, further research is necessary to clarify its role and potential combination with systemic treatments in TC management., Competing Interests: Declaration of Competing Interest None declared, (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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16. Synergistic Effects of Melatonin on Radiosensitization in Carbon-ion Radiotherapy.
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Ju M, Minami K, Katsuki S, Takenaka W, Tatekawa S, Tamari K, Koizumi M, Takahashi Y, and Ogawa K
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- Cell Line, Tumor, Mice, Animals, Humans, Cell Survival drug effects, Cell Survival radiation effects, Melanoma, Experimental radiotherapy, Melanoma, Experimental drug therapy, Melanoma, Experimental pathology, DNA Breaks, Double-Stranded drug effects, DNA Breaks, Double-Stranded radiation effects, Melatonin pharmacology, Heavy Ion Radiotherapy, Radiation Tolerance drug effects, DNA Repair drug effects, DNA Repair radiation effects, Radiation-Sensitizing Agents pharmacology
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Background/aim: Despite the established antitumor effectiveness and synergistic interactions of melatonin with photon irradiation, its role in carbon-ion radiotherapy remains uncertain. This study aimed to elucidate the mechanisms and potential clinical advantages of combining exogenous melatonin therapy with carbon-ion radiotherapy., Materials and Methods: The investigation assessed the impact of combining exogenous melatonin with photon or carbon-ion irradiation on cell-cycle modulation and DNA-repair capability using the melanoma cell line B16F10. RNA sequencing and bioinformatics analysis were conducted to explore mechanisms and evaluate potential clinical benefits, with validation performed on the osteosarcoma cell line LM8., Results: Pre-treatment with melatonin reduced the survival fraction of B16F10 and LM8 cells upon exposure to photon and carbon-ion radiation. Mechanistically, melatonin was found to inhibit G
2 /M arrest, preserve DNA damage, and suppress key genes involved in DNA double-strand break repair after 8 Gy carbon-ion radiation. Furthermore, RNA sequencing and bioinformatics analysis revealed favorable changes in genes associated with survival and metastasis, highlighting potential clinical significance. LM8 cells treated with melatonin exhibited increased radiosensitivity and suppression of DNA-repair proteins., Conclusion: The combination of exogenous melatonin not only heightened radiosensitivity and modulated hallmark tumor gene sets in vitro but also markedly suppressed the efficiency of DNA double-strand break-repair pathway, thus enhancing the cytotoxicity of carbon-ion radiotherapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)- Published
- 2024
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17. A dosiomics approach to treatment outcome modeling in carbon ion radiotherapy for skull base chordomas.
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Parrella G, Annunziata S, Morelli L, Molinelli S, Magro G, Ciocca M, Riva G, Ciccone LP, Iannalfi A, Paganelli C, Orlandi E, and Baroni G
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- Humans, Treatment Outcome, Male, Female, Middle Aged, Retrospective Studies, Radiometry, Adult, Aged, Radiotherapy Dosage, Linear Energy Transfer, Proportional Hazards Models, Neoplasm Recurrence, Local radiotherapy, Support Vector Machine, Chordoma radiotherapy, Skull Base Neoplasms radiotherapy, Heavy Ion Radiotherapy
- Abstract
Purpose: To investigate the role of dosiomics features extracted from physical dose (D
PHYS ), RBE-weighted dose (DRBE ) and dose-averaged Linear Energy Transfer (LETd ), to predict the risk of local recurrence (LR) in skull base chordoma (SBC) treated with Carbon Ion Radiotherapy (CIRT). Thus, define and evaluate dosiomics-driven tumor control probability (TCP) models., Materials and Methods: 54 SBC patients were retrospectively selected for this study. A regularized Cox proportional hazard model (r-Cox) and Survival Support Vector Machine (s-SVM) were tuned within a repeated Cross Validation (CV) and patients were stratified in low/high risk of LR. Models' performance was evaluated through Harrell's concordance statistic (C-index), and survival was represented through Kaplan-Meier (KM) curves. A multivariable logistic regression was fit to the selected feature sets to generate a dosiomics-driven TCP model for each map. These were compared to a reference model built with clinical parameters in terms of f-score and accuracy., Results: The LETd maps reached a test C-index of 0.750 and 0.786 with r-Cox and s-SVM, and significantly separated KM curves. DPHYS maps and clinical parameters showed promising CV outcomes with C-index above 0.8, despite a poorer performance on the test set and patients stratification. The LETd-based TCP showed a significatively higher f-score (0.67[0.52-0.70], median[IQR]) compared to the clinical model (0.4[0.32-0.63], p < 0.025), while DPHYS achieved a significatively higher accuracy (DPHYS : 0.73[0.65-0.79], Clinical: 0.6 [0.52-0.72])., Conclusion: This analysis supports the role of LETd as relevant source of prognostic factors for LR in SBC treated with CIRT. This is reflected in the TCP modeling, where LETd and DPHYS showed an improved performance with respect to clinical models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)- Published
- 2024
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18. Dosimetric study for breathing-induced motion effects in an abdominal pancreas phantom for carbon ion mini-beam radiotherapy.
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Stengl C, Muñoz ID, Arbes E, Rauth E, Christensen JB, Vedelago J, Runz A, Jäkel O, and Seco J
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- Humans, Monte Carlo Method, Movement, Abdomen radiation effects, Organs at Risk radiation effects, Pancreatic Neoplasms radiotherapy, Radiotherapy Dosage, Phantoms, Imaging, Heavy Ion Radiotherapy, Respiration, Radiometry, Pancreas radiation effects
- Abstract
Background: Particle mini-beam therapy exhibits promise in sparing healthy tissue through spatial fractionation, particularly notable for heavy ions, further enhancing the already favorable differential biological effectiveness at both target and entrance regions. However, breathing-induced organ motion affects particle mini-beam irradiation schemes since the organ displacements exceed the mini-beam structure dimensions, decreasing the advantages of spatial fractionation., Purpose: In this study, the impact of breathing-induced organ motion on the dose distribution was examined at the target and organs at risk(OARs) during carbon ion mini-beam irradiation for pancreatic cancer., Methods: As a first step, the carbon ion mini-beam pattern was characterized with Monte Carlo simulations. To analyze the impact of breathing-induced organ motion on the dose distribution of a virtual pancreas tumor as target and related OARs, the anthropomorphic Pancreas Phantom for Ion beam Therapy (PPIeT) was irradiated with carbon ions. A mini-beam collimator was used to deliver a spatially fractionated dose distribution. During irradiation, varying breathing motion amplitudes were induced, ranging from 5 to 15 mm. Post-irradiation, the 2D dose pattern was analyzed, focusing on the full width at half maximum (FWHM), center-to-center distance (ctc), and the peak-to-valley dose ratio (PVDR)., Results: The mini-beam pattern was visible within OARs, while in the virtual pancreas tumor a more homogeneous dose distribution was achieved. Applied motion affected the mini-beam pattern within the kidney, one of the OARs, reducing the PVDR from 3.78 ± $\pm$ 0.12 to 1.478 ± $\pm$ 0.070 for the 15 mm motion amplitude. In the immobile OARs including the spine and the skin at the back, the PVDR did not change within 3.4% comparing reference and motion conditions., Conclusions: This study provides an initial understanding of how breathing-induced organ motion affects spatial fractionation during carbon ion irradiation, using an anthropomorphic phantom. A decrease in the PVDR was observed in the right kidney when breathing-induced motion was applied, potentially increasing the risk of damage to OARs. Therefore, further studies are needed to explore the clinical viability of mini-beam radiotherapy with carbon ions when irradiating abdominal regions., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)
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- 2024
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19. Understanding Relative Biological Effectiveness and Clinical Outcome of Prostate Cancer Therapy Using Particle Irradiation: Analysis of Tumor Control Probability With the Modified Microdosimetric Kinetic Model.
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Besuglow J, Tessonnier T, Mein S, Eichkorn T, Haberer T, Herfarth K, Abdollahi A, Debus J, and Mairani A
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- Humans, Male, Probability, Androgen Antagonists therapeutic use, Organs at Risk radiation effects, Treatment Outcome, Models, Biological, Kinetics, Dose Fractionation, Radiation, Rectum radiation effects, Urinary Bladder radiation effects, Prostatic Neoplasms radiotherapy, Prostatic Neoplasms pathology, Relative Biological Effectiveness, Heavy Ion Radiotherapy, Proton Therapy methods, Radiotherapy Planning, Computer-Assisted methods
- Abstract
Purpose: Recent experimental studies and clinical trial results might indicate that-at least for some indications-continued use of the mechanistic model for relative biological effectiveness (RBE) applied at carbon ion therapy facilities in Europe for several decades (LEM-I) may be unwarranted. We present a novel clinical framework for prostate cancer treatment planning and tumor control probability (TCP) prediction based on the modified microdosimetric kinetic model (mMKM) for particle therapy., Methods and Materials: Treatment plans of 91 patients with prostate tumors (proton: 46, carbon ions: 45) applying 66 GyRBE [RBE = 1.1 for protons and LEM-I, (α/β)
x = 2.0 Gy, for carbon ions] in 20 fractions were recalculated using mMKM [(α/β)x = 3.1 Gy]). Based solely on the response data of photon-irradiated patient groups stratified according to risk and usage of androgen deprivation therapy, we derived parameters for an mMKM-based Poisson-TCP model. Subsequently, new carbon and helium ion plans, adhering to prescribed biological dose criteria, were generated. These were systematically compared with the clinical experience of Japanese centers employing an analogous fractionation scheme and existing proton plans., Results: mMKM predictions suggested significant biological dose deviation between the proton and carbon ion arms. Patients irradiated with protons received (3.25 ± 0.08) GyRBEmMKM /Fx, whereas patients treated with carbon ions received(2.51 ± 0.05) GyRBEmMKM /Fx. TCP predictions were (86 ± 3)% for protons and (52 ± 4)% for carbon ions, matching the clinical outcome of 85% and 50%. Newly optimized carbon ion plans, guided by the mMKM/TCP model, effectively replicated clinical data from Japanese centers. Using mMKM, helium ions exhibited similar target coverage as proton and carbon ions and improved rectum and bladder sparing compared with proton., Conclusions: Our mMKM-based model for prostate cancer treatment planning and TCP prediction was validated against clinical data for proton and carbon ion therapy, and its application was extended to helium ion therapy. Based on the data presented in this work, mMKM seems to be a good candidate for clinical biological calculations in carbon ion therapy for prostate cancer., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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20. Preliminary result of combined treatment with scanning carbon-ion radiotherapy and image-guided brachytherapy for locally advanced cervical adenocarcinoma.
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Tsuchida K, Yoshida D, Shima S, Kusunoki T, Takayama Y, Koge H, Kano K, Takakusagi Y, Mizoguchi N, Kamada T, Kusano Y, Kato H, and Katoh H
- Subjects
- Humans, Female, Middle Aged, Aged, Adult, Treatment Outcome, Retrospective Studies, Neoplasm Staging, Combined Modality Therapy, Uterine Cervical Neoplasms radiotherapy, Uterine Cervical Neoplasms pathology, Brachytherapy, Heavy Ion Radiotherapy, Adenocarcinoma radiotherapy, Adenocarcinoma pathology, Radiotherapy, Image-Guided
- Abstract
Although there is growing evidence of the efficacy of carbon-ion radiotherapy (CIRT) for locally advanced cervical adenocarcinoma, reports on combined treatment with CIRT and image-guided brachytherapy (IGBT) are scarce. We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics (2008) stage II-IVA locally advanced cervical adenocarcinoma who received combined scanning CIRT (sCIRT) and IGBT between April 2019 and March 2022. sCIRT consisted of whole-pelvic irradiation with 36 Gy (relative biological effectiveness [RBE]) in 12 fractions and subsequent local boost irradiation with 19.2 Gy (RBE) in 4 fractions. Three sessions of IGBT were administered after completion of sCIRT. Concurrent chemotherapy using weekly cisplatin (40 mg/m2/week) was also administered. Efficacy, toxicity and dose-volume parameters were analyzed. Fifteen patients were included in the analysis. The median follow-up period was 25 months. The 2-year overall survival, progression-free survival and local control rates were 92.3% (95% confidence interval [CI] = 77.8-100%), 52.5% (95% CI = 26.9-78.1%) and 84.8% (95% CI = 65.2-100%), respectively. Neither severe acute toxicity necessitating treatment cessation nor grade 3 or higher late toxicity were observed. The sigmoid D2cm3 of the patient who developed grade 2 late sigmoid hemorrhage was 65.6 Gy, which exceeded the standard deviation and target dose. The combination of sCIRT and IGBT for locally advanced cervical adenocarcinoma showed acceptable efficacy and safety. Further large-scale and long-term studies are warranted to confirm the efficacy and safety of this treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)
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- 2024
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21. A future directions of renal cell carcinoma treatment: combination of immune checkpoint inhibition and carbon ion radiotherapy.
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Zheng Z, Yang T, Li Y, Qu P, Shao Z, Wang Y, Chang W, Umar SM, Wang J, Ding N, and Wang W
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- Humans, Combined Modality Therapy, Animals, Immunotherapy methods, Carcinoma, Renal Cell therapy, Carcinoma, Renal Cell radiotherapy, Carcinoma, Renal Cell immunology, Immune Checkpoint Inhibitors therapeutic use, Heavy Ion Radiotherapy, Kidney Neoplasms therapy, Kidney Neoplasms radiotherapy, Kidney Neoplasms immunology
- Abstract
Renal cell carcinoma (RCC) is considered radio- and chemo-resistant. Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in advanced RCC. However, the overall response rate of RCC to monotherapy remains limited. Given its immunomodulatory effects, a combination of radiotherapy (RT) with immunotherapy is increasingly used for cancer treatment. Heavy ion radiotherapy, specifically the carbon ion radiotherapy (CIRT), represents an innovative approach to cancer treatment, offering superior physical and biological effectiveness compared to conventional photon radiotherapy and exhibiting obvious advantages in cancer treatment. The combination of CIRT and immunotherapy showed robust effectiveness in preclinical studies of various tumors, thus holds promise for overcoming radiation resistance of RCC and enhancing therapeutic outcomes. Here, we provide a comprehensive review on the biophysical effects of CIRT, the efficacy of combination treatment and the underlying mechanisms involved in, as well as its therapeutic potential specifically within RCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zheng, Yang, Li, Qu, Shao, Wang, Chang, Umar, Wang, Ding and Wang.)
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- 2024
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22. Transcriptomic response of prostate cancer cells to carbon ion and photon irradiation with focus on androgen receptor and TP53 signaling.
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Hänze J, Mengen LM, Mernberger M, Tiwari DK, Plagge T, Nist A, Subtil FSB, Theiss U, Eberle F, Roth K, Lauth M, Hofmann R, Engenhart-Cabillic R, Stiewe T, and Hegele A
- Subjects
- Humans, Male, Carbon, Cell Line, Tumor, DNA Damage radiation effects, DNA Repair, Gene Expression Regulation, Neoplastic radiation effects, Gene Expression Regulation, Neoplastic drug effects, Heavy Ion Radiotherapy, Photons, Prostatic Neoplasms radiotherapy, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Receptors, Androgen metabolism, Receptors, Androgen genetics, Signal Transduction radiation effects, Transcriptome radiation effects, Tumor Suppressor Protein p53 metabolism
- Abstract
Background: Radiotherapy is essential in the treatment of prostate cancer. An alternative to conventional photon radiotherapy is the application of carbon ions, which provide a superior intratumoral dose distribution and less induced damage to adjacent healthy tissue. A common characteristic of prostate cancer cells is their dependence on androgens which is exploited therapeutically by androgen deprivation therapy in the advanced prostate cancer stage. Here, we aimed to analyze the transcriptomic response of prostate cancer cells to irradiation by photons in comparison to carbon ions, focusing on DNA damage, DNA repair and androgen receptor signaling., Methods: Prostate cancer cell lines LNCaP (functional TP53 and androgen receptor signaling) and DU145 (dysfunctional TP53 and androgen receptor signaling) were irradiated by photons or carbon ions and the subsequent DNA damage was assessed by immuno-cytofluorescence. Furthermore, the cells were treated with an androgen-receptor agonist. The effects of irradiation and androgen treatment on the gene regulation and the transcriptome were investigated by RT-qPCR and RNA sequencing, followed by bioinformatic analysis., Results: Following photon or carbon ion irradiation, both LNCaP and DU145 cells showed a dose-dependent amount of visible DNA damage that decreased over time, indicating occurring DNA repair. In terms of gene regulation, mRNAs involved in the TP53-dependent DNA damage response were significantly upregulated by photons and carbon ions in LNCaP but not in DU145 cells, which generally showed low levels of gene regulation after irradiation. Both LNCaP and DU145 cells responded to photons and carbon ions by downregulation of genes involved in DNA repair and cell cycle, partially resembling the transcriptome response to the applied androgen receptor agonist. Neither photons nor carbon ions significantly affected canonical androgen receptor-dependent gene regulation. Furthermore, certain genes that were specifically regulated by either photon or carbon ion irradiation were identified., Conclusion: Photon and carbon ion irradiation showed a significant congruence in terms of induced signaling pathways and transcriptomic responses. These responses were strongly impacted by the TP53 status. Nevertheless, irradiation mode-dependent distinct gene regulations with undefined implication for radiotherapy outcome were revealed. Androgen receptor signaling and irradiations shared regulation of certain genes with respect to DNA-repair and cell-cycle., (© 2024. The Author(s).)
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- 2024
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23. A Phase Ib Study of Durvalumab (MEDI4736) in Combination with Carbon-Ion Radiotherapy and Weekly Cisplatin for Patients with Locally Advanced Cervical Cancer (DECISION Study): The Early Safety and Efficacy Results
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Noriyuki Okonogi, Kazutoshi Murata, Shigeru Yamada, Yuji Habu, Makoto Hori, Tomoya Kurokawa, Yosuke Inaba, Tadami Fujiwara, Yasuhisa Fujii, Michiko Hanawa, Yohei Kawasaki, Yoko Hattori, Kazuko Suzuki, Kyoko Tsuyuki, Masaru Wakatsuki, Masashi Koto, Sumitaka Hasegawa, Hitoshi Ishikawa, Hideki Hanaoka, Makio Shozu, Hiroshi Tsuji, and Hirokazu Usui
- Subjects
clinical trial ,radiotherapy ,heavy ion radiotherapy ,cisplatin ,durvalumab ,uterine cervical neoplasms ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m2. Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study.
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- 2023
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24. Is there a place for definitive radiotherapy in the treatment of unresectable soft-tissue sarcoma? A systematic review.
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Allignet, Benoît, Sunyach, Marie-Pierre, Geets, Xavier, and Waissi, Waisse
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- *
DRUG efficacy , *ONLINE information services , *SYSTEMATIC reviews , *TREATMENT effectiveness , *DESCRIPTIVE statistics , *RADIATION doses , *PROTON therapy , *RADIOTHERAPY , *MEDLINE , *SARCOMA , *PATIENT safety , *EVALUATION - Abstract
Definitive external beam radiotherapy (EBRT) is an unusual treatment of unresectable soft-tissue sarcomas (STS). Recent technical innovations and physical advantages of particle therapies may improve results of this therapeutic option. The role of this review was to report the clinical results of photon- and particle-based EBRT in unresectable STS. We performed a systematic review of the literature on Pubmed database to identify studies investigating the efficacy and safety of EBRT. The primary endpoint was local control (LC) and secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events in a subset of patients with gross disease STS. We identified 29 studies involving 1409 patients (pts) evaluating photon (n = 18; 956 pts), proton (n = 1; 21 pts), carbon ion (n = 2; 152 pts), neutron (n = 7; 259 pts) or pion (n = 1; 21 pts) therapy. Definitive EBRT achieves valuable 5-year LC rates of 28–73% with photon and 52–69% with particle therapies. Most local failures (66–100%) occurred within 3 years. Long-term disease control can be achieved in a fraction of patients, with 5-year PFS and OS of 0–39% and 24.7–63%, respectively. The rate of severe adverse events was highly variable with photons, <15% in proton and carbon ion therapy, whereas 25 to 50% of patients treated with neutrons and pions presented severe AE. While a dose higher or equal 64 Gy seem to improve the prognosis, delivering a dose higher or equal 68 Gy dramatically increases severe adverse events. Definitive EBRT with dose 64–66 Gy seems to be a safe and efficient treatment for unresectable STS. Future clinical trials should assess the potential of biomarkers of response, thus identifying patients that could benefit from local treatment. [ABSTRACT FROM AUTHOR]
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- 2022
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25. Comparison of carbon ion and photon reirradiation for recurrent glioblastoma.
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Lautenschlaeger, F. S., Dumke, R., Schymalla, M., Hauswald, H., Carl, B., Stein, M., Keber, U., Jensen, A., Engenhart-Cabillic, R., and Eberle, F.
- Abstract
Purpose: Purpose of this study was to investigate overall survival in recurrent glioblastoma treated with either carbon ion reirradiation or photon reirradiation. Materials and methods: In this retrospective study we evaluated 78 consecutive patients with recurrent IDH (Isocitrate dehydrogenase)-wildtype glioblastoma (38 patients carbon ion re-radiotherapy, 40 patients photon re-radiotherapy) treated with either carbon ion reirradiation or stereotactic photon reirradiation. 45 Gy (RBE; 15 fractions) carbon ion reirradiation (CIRT) or 39 Gy (13 fractions) photon reirradiation (FSRT) was administered, respectively. Overall survival was investigated with respect to histological, clinical, and epidemiological features. Kaplan–Meier and multivariate Cox statistics were calculated. A propensity score-matched analysis of the FSRT and CIRT groups using variables from a validated prognosis score was carried out. Results: The type of reirradiation (CIRT vs. FSRT) significantly influenced overall survival—8.0 months vs. 6.5 months (univariate: p = 0.046)—and remained an independent prognostic factor in multivariate analysis (p = 0.017). Propensity score-adjusted analysis with CIRT versus FSRT as the dependent variable yielded a significant overall survival advantage for the CIRT group (median OS 8.9 versus 7.2 months, p = 0.041, 1‑year survival 29 versus 10%). Adverse events (AE) were evaluated for both subgroups. For the FSRT group no toxicity ≥ grade 4 occurred. For the CIRT subgroup no grade 5 AE occurred, but 1 patient developed a grade 4 radionecrosis. We encountered 4 grade 3 toxicities. One patient developed a zoster at the trunk, 2 progressed in their paresis, and 1 featured progressive dysesthesia. Conclusion: In conclusion, carbon ion treatment is a safe and feasible treatment option for recurrent glioblastoma. Due to the retrospective nature of the study and two different dose levels for CIRT or FSRT, the improved outcome in CIRT reirradiation might be an effect of higher biological impact from carbon ions or a simple dose-escalation effect. This hypothesis needs prospective testing in larger patient cohorts. A prospective phase III randomized trial is in preparation at our center. [ABSTRACT FROM AUTHOR]
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- 2022
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26. Efficacy and Safety of 4 Fractions of Carbon-Ion Radiation Therapy for Hepatocellular Carcinoma: A Prospective Study.
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Shibuya, Kei, Katoh, Hiroyuki, Koyama, Yoshinori, Shiba, Shintaro, Okamoto, Masahiko, Okazaki, Shohei, Araki, Kenichiro, Kakizaki, Satoru, Shirabe, Ken, and Ohno, Tatsuya
- Subjects
RADIOTHERAPY ,LONGITUDINAL method ,LIVER cancer ,CANCER treatment ,TUMORS - Abstract
Introduction: Prospective evidence supporting the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for hepatocellular carcinoma (HCC) remains lacking. This prospective study aimed to evaluate the safety and efficacy of hypofractionated C-ion RT in patients with HCC. Methods: The inclusion criteria were as follows: (1) pathologically or clinically diagnosed HCC; (2) measurable tumor and tumor size ≤10 cm; (3) absence of major vascular invasion; (4) no extrahepatic metastasis; (5) the alimentary tract was not adjacent to the target lesion (>1 cm); (6) not suitable for or refusal to undergo surgery or local ablative therapies; (7) an interval ≥4 weeks from previous therapy; (8) no other intrahepatic lesion or at least 2 years after the previous curative therapy; (9) performance status score, 0–2; and (10) Child-Pugh score, 5–9. The prescribed C-ion RT dose was 52.8 Gy (relative biological effectiveness [RBE]) or 60.0 Gy (RBE) in 4 fractions. Results: In total, 35 patients with HCC were enrolled between October 2010 and May 2016. The median follow-up durations in the survivor group (n = 23) and in the whole cohort were 55.1 and 49.0 months, respectively. The 2-, 3-, and 4-year overall survival rates were 82.8%, 76.7%, and 69.4%, respectively. The 2-, 3-, and 4-year local control (LC) rates were 92.6%, 76.5%, and 76.5%, respectively. The median time-to-progression was 25.6 months (95% confidence interval, 13.7–37.5 months). Grade 4 or 5 toxicities were not observed. Grade 3 acute and late toxicities were observed in 2 patients. There was no significant deterioration in serum albumin, bilirubin, prothrombin time-international normalized ratio, platelet count, or Child-Pugh score after C-ion RT. Conclusion: Four fractions of C-ion RT for HCC did not yield serious adverse events and showed promising LC, thus making it a safe and effective modality for this type of malignancy. [ABSTRACT FROM AUTHOR]
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- 2022
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27. Editorial: Multifaceted Approaches Combining Low or High LET Radiation and Pharmacological Interventions in Cancer and Radioprotection: From Bench to Bedside
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Pankaj Chaudhary, Sandeep Kumar Shukla, and Shubhankar Suman
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radiotherapy ,cancer ,radioprotection ,radiosensitization ,heavy ion radiotherapy ,radiobiology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
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28. A treatment planning study of combined carbon ion-beam plus photon intensity-modulated radiotherapy
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Christopher Schuppert, Angela Paul, Simeon Nill, Andrea Schwahofer, Jürgen Debus, and Florian Sterzing
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Radiotherapy ,Combined modality therapy ,Heavy ion radiotherapy ,Radiotherapy, Intensity-modulated ,Radiotherapy planning ,Computer-assisted ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background and purpose: Combined photon intensity-modulated radiotherapy (IMRT) and sequential dose-escalated carbon ion beam therapy (IBT) is a technically advanced treatment option for head and neck malignancies. We proposed and evaluated an integrated planning strategy as opposed to an established and largely separated planning workflow. Materials and methods: Ten patients with representative malignancies of the head and neck region underwent combined carbon-photon radiotherapy (RT) in our facilities. Clinical plans were created according to the separated workflow with independent optimization stages for both modalities. Experimental plans incorporated the existing carbon IBT dose distribution into the optimization stage of a step-and-shoot photon IMRT (bias dose planning). Results: Cumulative dose distributions showed statistically significant differences between the two planning strategies and were predominantly in favor of the integrated approach. As such, target irradiation was generally maintained or even improved in a subset of metrics, while normal tissue sparing was widely enhanced; for instance, in the ipsilateral temporal lobe with median Dmean of −16% (p
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- 2020
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29. Hypofractionated carbon‐ion radiotherapy for stage I peripheral nonsmall cell lung cancer (GUNMA0701): Prospective phase II study
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Jun‐ichi Saitoh, Katsuyuki Shirai, Tatsuji Mizukami, Takanori Abe, Takeshi Ebara, Tatsuya Ohno, Koichi Minato, Ryusei Saito, Masanobu Yamada, and Takashi Nakano
- Subjects
carbon‐ion radiotherapy ,heavy ion radiotherapy ,nonsmall cell lung cancer ,phase II clinical trial ,prospective study ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract This phase II study's aim was to confirm the efficacy and safety of hypofractionated carbon‐ion radiotherapy in patients with stage I peripheral nonsmall cell lung cancer (NSCLC). The study encompassed 37 patients with histologically proven peripheral stage I NSCLC in the period June 2010‐March 2015. All underwent the planned full dose of carbon‐ion radiotherapy, administered with relative biological effectiveness of 52.8 Gy and 60 Gy (divided into four fractions over 1 week) for T1 and T2a tumors, respectively. The 2‐year local control rate was set as the primary endpoint, while overall survival, progression‐free survival, and the incidence rates of acute and late adverse events were secondary endpoints. The patients were followed up for 56.3 months overall and 62.2 months in the surviving patients, respectively. The actuarial local control rates were 91.2% after 2 years, and 88.1% after 5 years. No differences were found between the T1 and T2a tumors in the 5‐year local control rate (90.9% vs 86.7%, P = .75). The actuarial overall survival rates achieved 91.9% for 2‐year and 74.9% for 5‐year period. T1 tumors showed actuarial 5‐year overall survival rates of 80%, compared to 66.7% in T2a tumors. Two patients with T2a tumors and either severe emphysema or bronchiectasis experienced lung toxicity ≥ grade 2, in contrast to T1 patients who only experienced mild toxicities (lower than grade 2). The findings suggest that carbon‐ion radiotherapy is effective and safe for peripheral stage I NSCLC; however, further clinical evaluations are needed to confirm its therapeutic efficacy. Trial registration: UMIN000003797. Registered 21 June 2010, prospectively registered.
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- 2019
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30. Potential Benefits of Combining Proton or Carbon Ion Therapy with DNA Damage Repair Inhibitors.
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Rødland GE, Temelie M, Eek Mariampillai A, Hauge S, Gilbert A, Chevalier F, Savu DI, and Syljuåsen RG
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- Humans, Neoplasms drug therapy, Neoplasms radiotherapy, Animals, Linear Energy Transfer, DNA Repair drug effects, DNA Damage, Proton Therapy, Heavy Ion Radiotherapy
- Abstract
The use of charged particle radiotherapy is currently increasing, but combination therapy with DNA repair inhibitors remains to be exploited in the clinic. The high-linear energy transfer (LET) radiation delivered by charged particles causes clustered DNA damage, which is particularly effective in destroying cancer cells. Whether the DNA damage response to this type of damage is different from that elicited in response to low-LET radiation, and if and how it can be targeted to increase treatment efficacy, is not fully understood. Although several preclinical studies have reported radiosensitizing effects when proton or carbon ion irradiation is combined with inhibitors of, e.g., PARP, ATR, ATM, or DNA-PKcs, further exploration is required to determine the most effective treatments. Here, we examine what is known about repair pathway choice in response to high- versus low-LET irradiation, and we discuss the effects of inhibitors of these pathways when combined with protons and carbon ions. Additionally, we explore the potential effects of DNA repair inhibitors on antitumor immune signaling upon proton and carbon ion irradiation. Due to the reduced effect on healthy tissue and better immune preservation, particle therapy may be particularly well suited for combination with DNA repair inhibitors.
- Published
- 2024
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31. Comparison of linear energy transfer measurement for therapeutic carbon beam using CR-39 and TLD.
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Yuan Z, Zhuo W, Yang S, Li Z, Zhao J, and Chen B
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- Phantoms, Imaging, Carbon, Equipment Design, Polyethylene Glycols, Linear Energy Transfer, Thermoluminescent Dosimetry instrumentation, Heavy Ion Radiotherapy
- Abstract
The measurement of linear energy transfer (LET) is crucial for the evaluation of the radiation effect in heavy ion therapy. As two detectors which are convenient to implant into the phantom, the performance of CR-39 and thermoluminescence detector (TLD) for LET measurement was compared by experiment and simulation in this study. The results confirmed the applicability of both detectors for LET measurements, but also revealed that the CR-39 detector would lead to potential overestimation of dose-averaged LET compared with the simulation by PHITS, while the TLD would have a large uncertainty measuring ions with LET larger than 20 keV μ m
-1 . The results of this study were expected to improve the detection method of LET for therapeutic carbon beam and would finally be benefit to the quality assurance of heavy ion radiotherapy., (© 2024 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)- Published
- 2024
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32. 14-3-3σ downregulation sensitizes pancreatic cancer to carbon ions by suppressing the homologous recombination repair pathway.
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Wang D, Luo H, Chen Y, Ou Y, Dong M, Chen J, Liu R, Wang X, and Zhang Q
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- Animals, Humans, Mice, Cell Line, Tumor, Down-Regulation, Radiation Tolerance genetics, Exoribonucleases metabolism, Exoribonucleases genetics, Heavy Ion Radiotherapy, Carbon, Cell Proliferation genetics, Gene Expression Regulation, Neoplastic, Male, DNA Damage, Female, 14-3-3 Proteins metabolism, 14-3-3 Proteins genetics, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms radiotherapy, Recombinational DNA Repair, Mice, Inbred BALB C
- Abstract
This study explored the role of 14-3-3σ in carbon ion-irradiated pancreatic adenocarcinoma (PAAD) cells and xenografts and clarified the underlying mechanism. The clinical significance of 14-3-3σ in patients with PAAD was explored using publicly available databases. 14-3-3σ was silenced or overexpressed and combined with carbon ions to measure cell proliferation, cell cycle, and DNA damage repair. Immunoblotting and immunofluorescence (IF) assays were used to determine the underlying mechanisms of 14-3-3σ toward carbon ion radioresistance. We used the BALB/c mice to evaluate the biological behavior of 14-3-3σ in combination with carbon ions. Bioinformatic analysis revealed that PAAD expressed higher 14-3-3σ than normal pancreatic tissues; its overexpression was related to invasive clinicopathological features and a worse prognosis. Knockdown or overexpression of 14-3-3σ demonstrated that 14-3-3σ promoted the survival of PAAD cells after carbon ion irradiation. And 14-3-3σ was upregulated in PAAD cells during DNA damage (carbon ion irradiation, DNA damaging agent) and promotes cell recovery. We found that 14-3-3σ resulted in carbon ion radioresistance by promoting RPA2 and RAD51 accumulation in the nucleus in PAAD cells, thereby increasing homologous recombination repair (HRR) efficiency. Blocking the HR pathway consistently reduced 14-3-3σ overexpression-induced carbon ion radioresistance in PAAD cells. The enhanced radiosensitivity of 14-3-3σ depletion on carbon ion irradiation was also demonstrated in vivo . Altogether, 14-3-3σ functions in tumor progression and can be a potential target for developing biomarkers and treatment strategies for PAAD along with incorporating carbon ion irradiation.
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- 2024
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33. DNA-PKcs Inhibition Sensitizes Human Chondrosarcoma Cells to Carbon Ion Irradiation via Cell Cycle Arrest and Telomere Capping Disruption.
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Lohberger B, Barna S, Glänzer D, Eck N, Leithner A, and Georg D
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- Humans, Cell Line, Tumor, Cell Cycle Checkpoints drug effects, Cell Cycle Checkpoints radiation effects, DNA Repair drug effects, Radiation Tolerance drug effects, Pyrazoles pharmacology, Cell Proliferation drug effects, Bone Neoplasms metabolism, Bone Neoplasms genetics, Bone Neoplasms pathology, Bone Neoplasms drug therapy, G2 Phase Cell Cycle Checkpoints drug effects, G2 Phase Cell Cycle Checkpoints radiation effects, DNA-Activated Protein Kinase antagonists & inhibitors, DNA-Activated Protein Kinase metabolism, DNA-Activated Protein Kinase genetics, Chondrosarcoma metabolism, Chondrosarcoma genetics, Chondrosarcoma radiotherapy, Chondrosarcoma drug therapy, Heavy Ion Radiotherapy, Telomere drug effects, Telomere metabolism
- Abstract
In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor AZD7648 was explored for carbon ion (C-ion) as well as reference photon (X-ray) irradiation (IR) using gene expression analysis, flow cytometry, protein phosphorylation, and telomere length shortening. Proliferation markers and cell cycle distribution changed significantly after combined treatment, revealing a prominent G
2 /M arrest. The expression of the G2 /M checkpoint genes cyclin B, CDK1, and WEE1 was significantly reduced by IR alone and the combined treatment. While IR alone showed no effects, additional AZD7648 treatment resulted in a dose-dependent reduction in AKT phosphorylation and an increase in Chk2 phosphorylation. Twenty-four hours after IR, the key genes of DNA repair mechanisms were reduced by the combined treatment, which led to impaired DNA repair and increased radiosensitivity. A time-dependent shortening of telomere length was observed in both cell lines after combined treatment with AZD7648 and 8 Gy X-ray/C-ion IR. Our data suggest that the inhibition of DNA-PKcs may increase sensitivity to X-rays and C-ion IR by impairing its functional role in DNA repair mechanisms and telomere end protection.- Published
- 2024
- Full Text
- View/download PDF
34. Nanodosimetric quantity-weighted dose optimization for carbon-ion treatment planning.
- Author
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Yang J, Liu X, Zhang H, Dai Z, He P, Ma Y, Shen G, Chen W, and Li Q
- Subjects
- Humans, Radiometry, Nanotechnology, Relative Biological Effectiveness, Algorithms, Dose-Response Relationship, Radiation, Radiotherapy Planning, Computer-Assisted, Carbon chemistry, Radiotherapy Dosage, Heavy Ion Radiotherapy
- Abstract
Dose verification of treatment plans is an essential step in radiotherapy workflows. In this work, we propose a novel method of treatment planning based on nanodosimetric quantity-weighted dose (NQWD), which could realize biological representation using pure physical quantities for biological-oriented carbon ion-beam treatment plans and their direct verification. The relationship between nanodosimetric quantities and relative biological effectiveness (RBE) was studied with the linear least-squares method for carbon-ion radiation fields. Next, under the framework of the matRad treatment planning platform, NQWD was optimized using the existing RBE-weighted dose (RWD) optimization algorithm. The schemes of NQWD-based treatment planning were compared with the RWD treatment plans in term of the microdosimetric kinetic model (MKM). The results showed that the nanodosimetric quantity F
3 - 10 had a good correlation with the radiobiological effect reflected by the relationship between RBE and F3 - 10 . Moreover, the NQWD-based treatment plans reproduced the RWD plans generally. Therefore, F3 - 10 could be adopted as a radiation quality descriptor for carbon-ion treatment planning. The novel method proposed herein not only might be helpful for rapid physical verification of biological-oriented ion-beam treatment plans with the development of experimental nanodosimetry, but also makes the direct comparison of ion-beam treatment plans in different institutions possible. Thus, our proposed method might be potentially developed to be a new strategy for carbon-ion treatment planning and improve patient safety for carbon-ion radiotherapy., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)- Published
- 2024
- Full Text
- View/download PDF
35. Inter-fractional error and intra-fractional motion of prostate and dosimetry comparisons of patient position registrations with versus without fiducial markers during treatment with carbon-ion radiotherapy.
- Author
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Iwai Y, Mori S, Ishikawa H, Kanematsu N, Matsumoto S, Nakaji T, Okonogi N, Kobayashi K, Wakatsuki M, Uno T, and Yamada S
- Subjects
- Humans, Male, Radiometry, Radiotherapy Dosage, Prostate radiation effects, Prostate diagnostic imaging, Aged, Motion, Dose Fractionation, Radiation, Fiducial Markers, Prostatic Neoplasms radiotherapy, Prostatic Neoplasms diagnostic imaging, Patient Positioning, Heavy Ion Radiotherapy, Radiotherapy Planning, Computer-Assisted methods, Movement
- Abstract
A few reports have discussed the influence of inter-fractional position error and intra-fractional motion on dose distribution, particularly regarding a spread-out Bragg peak. We investigated inter-fractional and intra-fractional prostate position error by monitoring fiducial marker positions. In 2020, data from 15 patients with prostate cancer who received carbon-ion beam radiotherapy (CIRT) with gold markers were investigated. We checked marker positions before and during irradiation to calculate the inter-fractional positioning and intra-fractional movement and evaluated the CIRT dose distribution by adjusting the planning beam isocenter and clinical target volume (CTV) position. We compared the CTV dose coverages (CTV receiving 95% [V95%] or 98% [V98%] of the prescribed dose) between skeletal and fiducial matching irradiation on the treatment planning system. For inter-fractional error, the mean distance between the marker position in the planning images and that in a patient starting irradiation with skeletal matching was 1.49 ± 1.11 mm (95th percentile = 1.85 mm). The 95th percentile (maximum) values of the intra-fractional movement were 0.79 mm (2.31 mm), 1.17 mm (2.48 mm), 1.88 mm (4.01 mm), 1.23 mm (3.00 mm), and 2.09 mm (8.46 mm) along the lateral, inferior, superior, dorsal, and ventral axes, respectively. The mean V95% and V98% were 98.2% and 96.2% for the skeletal matching plan and 99.5% and 96.8% for the fiducial matching plan, respectively. Fiducial matching irradiation improved the CTV dose coverage compared with skeletal matching irradiation for CIRT for prostate cancer., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)
- Published
- 2024
- Full Text
- View/download PDF
36. Monte carlo simulation study on the dose and dose-averaged linear energy transfer distributions in carbon ion radiotherapy.
- Author
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Ishikawa A, Koba Y, Furuta T, Chang W, Yonai S, Matsumoto S, Hashimoto S, Hirai Y, and Sato T
- Subjects
- Radiation Dosage, Radiotherapy Planning, Computer-Assisted methods, Water chemistry, Monte Carlo Method, Linear Energy Transfer, Radiotherapy Dosage, Heavy Ion Radiotherapy
- Abstract
Dose-averaged linear energy transfer (LET
d ) is conventionally evaluated from the relative biological effectiveness (RBE)-LETd fitted function used in the treatment planning system. In this study, we calculated the physical doses and their linear energy transfer (LET) distributions for patterns of typical CIRT beams using Monte Carlo (MC) simulation. The LETd was then deduced from the MC simulation and compared with that obtained from the conventional method. The two types of LETd agreed well with each other, except around the distal end of the spread-out Bragg peak. Furthermore, an MC simulation was conducted with the material composition of water and realistic materials. The profiles of physical dose and LETd were in good agreement for both techniques. These results indicate that the previous studies to analyze the minimum LETd in CIRT cases are valid for practical situations, and the material composition conversion to water little affects the dose distribution in the irradiation field., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)- Published
- 2024
- Full Text
- View/download PDF
37. Tissue equivalent conversion of silicon-based microdosemeters in hadron therapy.
- Author
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Yu S, Shi H, and Zhong X
- Subjects
- Humans, Heavy Ion Radiotherapy, Phantoms, Imaging, Radiotherapy Dosage, Radiometry methods, Radiometry instrumentation, Equipment Design, Fourier Analysis, Silicon chemistry
- Abstract
Silicon has been developed as a microdosemeter, as it can provide sensitive volumes at submicrometric levels, does not need a gas supply, has a fast response, and has low power consumption. However, since the energy response in silicon is not the same as that in tissue, a spectral conversion from silicon to tissue is necessary to obtain the probability distribution of energy deposition in tissue. In this work, we present a method for microdosimetric spectra conversion from silicon to tissue based on the scaled Fourier transformation and the geometric scaling factor, which shows relatively good results in the spectral conversion from diamond to tissue. The results illustrate that the method can convert the energy deposition spectra from silicon to tissue with proper accuracy. Meanwhile, the inconsistency between the converted and actual spectra due to the inherent difference was also observed. Whereas, the reasons for the disagreement are different. For the plateau part of the Bragg curve, the discrepancy between the converted and actual spectra is due to the poor tissue equivalent of silicon. For the proximal part of the Bragg curve, the spectral difference is attributed to the different shapes of the energy deposition spectra obtained in silicon and water, which is the same as that in the diamond. In summary, this method can be employed in the tissue equivalent conversion of silicon microdosemeter, but the poor tissue equivalent of silicon limited the accuracy of this method. In addition, the correction for the deviation between the converted and calculated spectra due to the difference in spectral shapes is required to improve the practicality of this mod., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
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- View/download PDF
38. Modeling of the resensitization effect on carbon-ion radiotherapy for stage I non-small cell lung cancer.
- Author
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Inaniwa T, Kanematsu N, and Nakajima M
- Subjects
- Humans, Neoplasm Staging, Models, Biological, Radiation Tolerance, Carcinoma, Non-Small-Cell Lung radiotherapy, Lung Neoplasms radiotherapy, Heavy Ion Radiotherapy
- Abstract
Objective . To investigate the effect of redistribution and reoxygenation on the 3-year tumor control probability (TCP) of patients with stage I non-small cell lung cancer (NSCLC) treated with carbon-ion radiotherapy. Approach . A meta-analysis of published clinical data of 233 NSCLC patients treated by carbon-ion radiotherapy under 18-, 9-, 4-, and single-fraction schedules was conducted. The linear-quadratic (LQ)-based cell-survival model incorporating the radiobiological 5Rs, radiosensitivity, repopulation, repair, redistribution, and reoxygenation, was developed to reproduce the clinical TCP data. Redistribution and reoxygenation were regarded together as a single phenomenon and termed 'resensitization' in the model. The optimum interval time between fractions was investigated for each fraction schedule using the determined model parameters. Main results. The clinical TCP data for 18-, 9-, and 4-fraction schedules were reasonably reproduced by the model without the resensitization effect, whereas its incorporation was essential to reproduce the TCP data for all fraction schedules including the single fraction. The curative dose for the single-fraction schedule was estimated to be 49.0 Gy (RBE), which corresponds to the clinically adopted dose prescription of 50.0 Gy (RBE). For 18-, 9-, and 4-fraction schedules, a 2-to-3-day interval is required to maximize the resensitization effect during the time interval. In contrast, the single-fraction schedule cannot benefit from the resensitization effect, and the shorter treatment time is preferable to reduce the effect of sub-lethal damage repair during the treatment. Significance. The LQ-based cell-survival model incorporating the radiobiological 5Rs was developed and used to evaluate the effect of the resensitization on clinical results of NSCLC patients treated with hypo-fractionated carbon-ion radiotherapy. The incorporation of the resensitization into the cell-survival model improves the reproducibility to the clinical TCP data. A shorter treatment time is preferable in the single-fraction schedule, while a 2-to-3-day interval between fractions is preferable in the multi-fraction schedules for effective treatments., (© 2024 Institute of Physics and Engineering in Medicine.)
- Published
- 2024
- Full Text
- View/download PDF
39. The Use of Proton and Carbon Ion Radiation Therapy for Sarcomas.
- Author
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Ioakeim-Ioannidou M, Rose M, Chen YL, and MacDonald SM
- Subjects
- Humans, Protons, Heavy Ion Radiotherapy, Sarcoma radiotherapy, Proton Therapy
- Abstract
The unique physical and biological characteristics of proton and carbon ions allow for improved sparing of normal tissues, decreased integral dose to the body, and increased biological effect through high linear energy transfer. These properties are particularly useful for sarcomas given their histology, wide array of locations, and age of diagnosis. This review summarizes the literature and describes the clinical situations in which these heavy particles have advantages for treating sarcomas., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
40. The rationale for a carbon ion radiation therapy facility in Australia.
- Author
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Thwaites DI, Prokopovich DA, Garrett RF, Haworth A, Rosenfeld A, and Ahern V
- Subjects
- Protons, Australia, Ions, Heavy Ion Radiotherapy, Proton Therapy
- Abstract
Australia has taken a collaborative nationally networked approach to achieve particle therapy capability. This supports the under-construction proton therapy facility in Adelaide, other potential proton centres and an under-evaluation proposal for a hybrid carbon ion and proton centre in western Sydney. A wide-ranging overview is presented of the rationale for carbon ion radiation therapy, applying observations to the case for an Australian facility and to the clinical and research potential from such a national centre., (© 2023 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)
- Published
- 2024
- Full Text
- View/download PDF
41. An investigation of neutron shielding and activation performances of four types of concrete for carbon ion therapy facility.
- Author
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Yang Y, Ma F, Zhou X, Li W, Su Y, Xu C, and Jiang B
- Subjects
- Ions, Radioisotopes, Carbon, Monte Carlo Method, Radiation Dosage, Neutrons, Heavy Ion Radiotherapy
- Abstract
Carbon ions have unique physical and biological properties that allow for precise targeting of tumors while minimizing damage to surrounding healthy tissues. The emitted neutrons dominate the radiation field in the treatment room and pose challenges for radiological shielding. Concrete is extensively utilized in the construction of radiotherapy facilities due to its good shielding characteristics, and it can be easily poured into the desired shapes and thickness. The difference in composition of concrete affects the characteristics of neutron attenuation and activation performance. Therefore, the purpose of this study is to clarify the shielding properties and activation performances of four types of concrete for carbon ion therapy facilities. The Monte Carlo method is used to analyze the neutron spectra from thick targets upon carbon ion bombardment. Furthermore, the deep attenuation efficiency of the secondary neutron in different compositions of concrete is discussed. The shielding design is developed to ensure compliance with the prescribed dose limit outside the shielding during operation. Finally, the induced radioactivity in concrete is estimated for both short-term and long-term operation. The produced radionuclides inventories and depth profiling are determined. This study reveals the shielding and radioactivity issue of carbon ion therapy facilities and is expected to aid in the design or construction of similar facilities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
- Published
- 2024
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- View/download PDF
42. Visualized Analysis of Heavy Ion Radiotherapy: Development, Barriers and Future Directions.
- Author
-
Jin, Yuanchang, Li, Jingwen, Li, Jieyun, Zhang, Na, Guo, Kangle, Zhang, Qiuning, Wang, Xiaohu, and Yang, Kehu
- Subjects
HEAVY ions ,ION analysis ,CITATION analysis ,RADIOTHERAPY - Abstract
Background: Heavy ion radiotherapy (HIRT) has great advantages as tumor radiotherapy. Methods: Based on 1,558 literatures from core collections of Web of Science from 1980 to 2020, this study visually analyzes the evolution of HIRT research, and sorts out the hotspots and trends of HIRT research using CiteSpace software. Results: Research on HIRT has received more extensive attention over the last 40 years. The development of HIRT is not only closely related to radiation and oncology, but also closely related to the development of human society. In terms of citation frequency, "International Journal of Radiation Oncology*Biology*Physics" was the top journal. In terms of influence, "Radiotherapy and Oncology" was the top journal. "Radiation therapy" and "carbon ion radiotherapy" were the two most frequently used keywords in this field. Conclusion: The evolution of the HIRT research has occurred in approximately three stages, including technological exploration, safety and effectiveness research and technological breakthroughs. Finally, some suggestions for future research are put forward. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
43. Application of Carbon Ion and Its Sensitizing Agent in Cancer Therapy: A Systematic Review.
- Author
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Wang, Xiaolin, Chen, Xiaojun, Li, Guangfei, Han, Xiao, Gao, Tianxin, Liu, Weifeng, and Tang, Xiaoying
- Subjects
CANCER treatment ,HEAVY ions ,RADIOTHERAPY ,CARBON ,IONS - Abstract
Carbon ion radiation therapy (CIRT) is the most advanced radiation therapy (RT) available and offers new opportunities to improve cancer treatment and research. CIRT has a unique physical and biological advantage that allow them to kill tumor cells more accurately and intensively. So far, CIRT has been used in almost all types of malignant tumors, and showed good feasibility, safety and acceptable toxicity, indicating that CIRT has a wide range of development and application prospects. In addition, in order to improve the biological effect of CIRT, scientists are also trying to investigate related sensitizing agents to enhance the killing ability of tumor cells, which has attracted extensive attention. In this review, we tried to systematically review the rationale, advantages and problems, the clinical applications and the sensitizing agents of the CIRT. At the same time, the prospects of the CIRT in were prospected. We hope that this review will help researchers interested in CIRT, sensitizing agents, and radiotherapy to understand their magic more systematically and faster, and provide data reference and support for bioanalysis, clinical medicine, radiotherapy, heavy ion therapy, and nanoparticle diagnostics. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
44. Research on photogrammetry-based positioning of heavy ion radiotherapy and tumor target monitoring.
- Author
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Chen, W. J., Yang, Y. Q., Zheng, Y. J., Zhang, B., Wang, S. M., Yuan, J. D., Sun, G. Z., Zhang, X. D., and Yan, L. S.
- Subjects
- *
HEAVY ions , *DIGITAL photogrammetry , *RADIOTHERAPY , *PATIENT positioning , *TREATMENT effectiveness - Abstract
Heavy ion therapy is currently recognized as the most advanced cancer radiotherapy approach in the world. This article introduces a high-precision and non-contact measurement method based on close-range photogrammetry combined with a 3D control network of a laser tracker, which is used to guide the positioning and real-time target area monitoring for patients undergoing heavy ion radiotherapy. By the precise connection between the 3D control network of the laser tracker and the digital photogrammetry device, we position the photogrammetry system absolutely at the treatment isocenter, measuring the feature points of the target area on the patient's body surface. After that, the seven-parameter solution model is combined with the feature points to accurately determine the tumor position, as well as displaying its real-time location changes in the form of relative position to the treatment isocenter shown as six-degree-of-freedom parameters during radiotherapy, so that the patient may be guided to achieve a more reliable and efficient positioning. The research and design on the dual-camera close-range photogrammetry patient monitoring system has provided insights in the course of radiotherapy. That is to say, by monitoring the feature points on the patient's body surface, a real-time display of tumor displacement and a warning system for out-of-tolerance variances are established, controlling the treatment bed to stay on the tumor. This method could ensure the irradiation precision for the patient during the treatment and protect normal tissues from radiation exposure, optimizing the treatment outcome. Multiple patient positioning simulations have verified that the measurement precision of our photogrammetry-based method can meet the requirements of heavy ion radiotherapy patient positioning. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
45. Head and Neck Cancers, Version 1.2015.
- Author
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Pfister, David G, Spencer, Sharon, Brizel, David M, Burtness, Barbara, Busse, Paul M, Caudell, Jimmy J, Cmelak, Anthony J, Colevas, A Dimitrios, Dunphy, Frank, Eisele, David W, Foote, Robert L, Gilbert, Jill, Gillison, Maura L, Haddad, Robert I, Haughey, Bruce H, Hicks, Wesley L, Hitchcock, Ying J, Jimeno, Antonio, Kies, Merrill S, Lydiatt, William M, Maghami, Ellie, McCaffrey, Thomas, Mell, Loren K, Mittal, Bharat B, Pinto, Harlan A, Ridge, John A, Rodriguez, Cristina P, Samant, Sandeep, Shah, Jatin P, Weber, Randal S, Wolf, Gregory T, Worden, Frank, Yom, Sue S, McMillian, Nicole, and Hughes, Miranda
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Dental/Oral and Craniofacial Disease ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Carbon ,Guidelines as Topic ,Head and Neck Neoplasms ,Heavy Ion Radiotherapy ,Humans ,Neutron Capture Therapy ,Proton Therapy ,Oncology & Carcinogenesis ,Oncology and carcinogenesis ,Health services and systems - Abstract
These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.
- Published
- 2015
46. Carbon ion radiotherapy in Japan: an assessment of 20 years of clinical experience.
- Author
-
Kamada, Tadashi, Tsujii, Hirohiko, Blakely, Eleanor A, Debus, Jürgen, De Neve, Wilfried, Durante, Marco, Jäkel, Oliver, Mayer, Ramona, Orecchia, Roberto, Pötter, Richard, Vatnitsky, Stanislav, and Chu, William T
- Subjects
Humans ,Neoplasms ,Carbon ,Time Factors ,Japan ,Heavy Ion Radiotherapy ,Oncology & Carcinogenesis ,Oncology and Carcinogenesis - Abstract
Charged particle therapy is generally regarded as cutting-edge technology in oncology. Many proton therapy centres are active in the USA, Europe, and Asia, but only a few centres use heavy ions, even though these ions are much more effective than x-rays owing to the special radiobiological properties of densely ionising radiation. The National Institute of Radiological Sciences (NIRS) Chiba, Japan, has been treating cancer with high-energy carbon ions since 1994. So far, more than 8000 patients have had this treatment at NIRS, and the centre thus has by far the greatest experience in carbon ion treatment worldwide. A panel of radiation oncologists, radiobiologists, and medical physicists from the USA and Europe recently completed peer review of the carbon ion therapy at NIRS. The review panel had access to the latest developments in treatment planning and beam delivery and to all updated clinical data produced at NIRS. A detailed comparison with the most advanced results obtained with x-rays or protons in Europe and the USA was then possible. In addition to those tumours for which carbon ions are known to produce excellent results, such as bone and soft-tissue sarcoma of the skull base, head and neck, and pelvis, promising data were obtained for other tumours, such as locally recurrent rectal cancer and pancreatic cancer. The most serious impediment to the worldwide spread of heavy ion therapy centres is the high initial capital cost. The 20 years of clinical experience at NIRS can help guide strategic decisions on the design and construction of new heavy ion therapy centres.
- Published
- 2015
47. Application of Carbon Ion and Its Sensitizing Agent in Cancer Therapy: A Systematic Review
- Author
-
Xiaolin Wang, Xiaojun Chen, Guangfei Li, Xiao Han, Tianxin Gao, Weifeng Liu, and Xiaoying Tang
- Subjects
heavy ion radiotherapy ,carbon therapy ,radiation therapy ,clinical application ,sensitizing agent ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Carbon ion radiation therapy (CIRT) is the most advanced radiation therapy (RT) available and offers new opportunities to improve cancer treatment and research. CIRT has a unique physical and biological advantage that allow them to kill tumor cells more accurately and intensively. So far, CIRT has been used in almost all types of malignant tumors, and showed good feasibility, safety and acceptable toxicity, indicating that CIRT has a wide range of development and application prospects. In addition, in order to improve the biological effect of CIRT, scientists are also trying to investigate related sensitizing agents to enhance the killing ability of tumor cells, which has attracted extensive attention. In this review, we tried to systematically review the rationale, advantages and problems, the clinical applications and the sensitizing agents of the CIRT. At the same time, the prospects of the CIRT in were prospected. We hope that this review will help researchers interested in CIRT, sensitizing agents, and radiotherapy to understand their magic more systematically and faster, and provide data reference and support for bioanalysis, clinical medicine, radiotherapy, heavy ion therapy, and nanoparticle diagnostics.
- Published
- 2021
- Full Text
- View/download PDF
48. Visualized Analysis of Heavy Ion Radiotherapy: Development, Barriers and Future Directions
- Author
-
Yuanchang Jin, Jingwen Li, Jieyun Li, Na Zhang, Kangle Guo, Qiuning Zhang, Xiaohu Wang, and Kehu Yang
- Subjects
heavy ion radiotherapy ,Citespace ,visualization research ,cancer ,radiation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundHeavy ion radiotherapy (HIRT) has great advantages as tumor radiotherapy.MethodsBased on 1,558 literatures from core collections of Web of Science from 1980 to 2020, this study visually analyzes the evolution of HIRT research, and sorts out the hotspots and trends of HIRT research using CiteSpace software.ResultsResearch on HIRT has received more extensive attention over the last 40 years. The development of HIRT is not only closely related to radiation and oncology, but also closely related to the development of human society. In terms of citation frequency, “International Journal of Radiation Oncology*Biology*Physics” was the top journal. In terms of influence, “Radiotherapy and Oncology” was the top journal. “Radiation therapy” and “carbon ion radiotherapy” were the two most frequently used keywords in this field.ConclusionThe evolution of the HIRT research has occurred in approximately three stages, including technological exploration, safety and effectiveness research and technological breakthroughs. Finally, some suggestions for future research are put forward.
- Published
- 2021
- Full Text
- View/download PDF
49. Neue Entwicklungen in der pädiatrischen Radioonkologie.
- Author
-
Dieckmann, K., Dietzsch, S., Timmermann, B., and Kortmann, R.
- Abstract
Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2021
- Full Text
- View/download PDF
50. Differential response of esophageal cancer cells to particle irradiation
- Author
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Sarah Hartfiel, Matthias Häfner, Ramon Lopez Perez, Alexander Rühle, Thuy Trinh, Jürgen Debus, Peter E. Huber, and Nils H. Nicolay
- Subjects
Esophageal cancer ,Proton radiation ,Carbon ion radiation ,Heavy ion radiotherapy ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Radiation therapy is a mainstay in the treatment of esophageal cancer (EC) patients, and photon radiotherapy has proved beneficial both in the neoadjuvant and the definitive setting. However, regarding the still poor prognosis of many EC patients, particle radiation employing a higher biological effectiveness may help to further improve patient outcomes. However, the influence of clinically available particle radiation on EC cells remains largely unknown. Methods Patient-derived esophageal adenocarcinoma and squamous cell cancer lines were treated with photon and particle irradiation using clinically available proton (1H), carbon (12C) or oxygen (16O) beams at the Heidelberg Ion Therapy Center. Histology-dependent clonogenic survival was calculated for increasing physical radiation doses, and resulting relative biological effectiveness (RBE) was calculated for each radiation modality. Cell cycle effects caused by photon and particle radiation were assessed, and radiation-induced apoptosis was measured in adenocarcinoma and squamous cell EC samples by activated caspase-3 and sub-G1 populations. Repair kinetics of DNA double strand breaks induced by photon and particle radiation were investigated. Results While both adenocarcinoma EC cell lines demonstrated increasing sensitivities for 1H, 12C and 16O radiation, the two squamous cell carcinoma lines exhibited a more heterogeneous response to photon and particle treatment; average RBE values were calculated as 1.15 for 1H, 2.3 for 12C and 2.5 for 16O irradiation. After particle irradiation, squamous cell EC samples reacted with an increased and prolonged block in G2 phase of the cell cycle compared to adenocarcinoma cells. Particle radiation resulted in an incomplete repair of radiation-induced DNA double strand breaks in both adenocarcinoma and squamous cell carcinoma samples, with the levels of initial strand break induction correlating well with the individual cellular survival after photon and particle radiation. Similarly, EC samples demonstrated heterogeneous levels of radiation-induced apoptosis that also corresponded to the observed cellular survival of individual cell lines. Conclusions Esophageal cancer cells exhibit differential responses to irradiation with photons and 1H, 12C and 16O particles that were independent of tumor histology. Therefore, yet unknown molecular markers beyond histology may help to establish which esophageal cancer patients benefit from the biological effects of particle treatment.
- Published
- 2019
- Full Text
- View/download PDF
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