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BACKGROUND: Nasopharyngeal adenoid cystic carcinoma (NACC) is a relatively rare salivary gland tumor that is generally associated with poor outcomes. High-dose radiotherapy is a key treatment for patients with NACC. This study reported the long-term efficacy and safety of particle beam radiation therapy (PBRT) for NACC. METHODS AND MATERIALS: Twenty-six patients with nonmetastatic NACC who received definitive PBRT alone were included in this retrospective study. The majority of patients (92.3%) had locally advanced disease. Twenty-five (96.15%) patients received intensity-modulated proton radiotherapy (IMPT) followed by a carbon ion radiotherapy (CIRT) boost, and one patient received CIRT alone. Overall survival (OS), local control (LC), regional control (RC), and distant metastasis control (DMC) rates were calculated via the Kaplan-Meier method. RESULTS: The median follow-up time was 46.95 months for the entire cohort. Seven patients experienced local recurrence, and one patient experience neck lymph node recurrence. The 3- and 4-year OS, LC, RC, and DMC rates were 100% and 91.7%, 92.3% and 84.6%, 95.8% and 87.8%, and 90.2% and 71.3%, respectively. A total of 91.3% of the patients achieved complete remission of gross tumors at 1 year after PBRT. Severe acute toxicity was observed in only two patients. A grade 4 decrease in visual acuity was observed in one patient with orbital apex invasion. No late grade 3 or 5 toxicity was observed. CONCLUSION: Definitive PBRT provided a satisfactory 4-year OS for patients with locally advanced NACC. The toxicity was acceptable and mild. Further follow-up is necessary to confirm the efficacy and safety of definitive PBRT for patients with NACC.

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Carcinoma Adenoide Quístico , Neoplasias Nasofaríngeas , Terapia de Protones , Humanos , Carcinoma Adenoide Quístico/radioterapia , Carcinoma Adenoide Quístico/mortalidad , Carcinoma Adenoide Quístico/patología , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Adulto , Estudios Retrospectivos , Resultado del Tratamiento , Anciano , Terapia de Protones/efectos adversos , Terapia de Protones/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Adulto Joven , Estudios de Seguimiento , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Recurrencia Local de Neoplasia/radioterapia , Radioterapia de Iones Pesados/efectos adversos , Radioterapia de Iones Pesados/métodos

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Background: Hypoxia is the bottleneck that affects the response of conventional photon radiotherapy, but it does not seem to have much effect on carbon ion radiotherapy (CIRT). This study aimed to evaluate the changes of hypoxia before and after CIRT in patients with non-small cell lung cancer (NSCLC) and whether 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) imaging could predict the response to CIRT in NSCLC patients. Methods: A total of 29 patients with NSCLC who received CIRT were retrospectively included. 18F-FMISO PET/CT imaging was performed before and after treatment, and chest CT was performed after radiotherapy. Radiation response within 1 week after radiotherapy and at the initial follow-up were defined as the immediate response (IR) and early response (ER), respectively. The tumor-to-muscle ratio (TMR), hypoxia volume (HV), and the ΔTMR and ΔHV values of 18F-FMISO uptake were collected. Fisher's exact test, Mann-Whitney U test, Wilcoxon signed-rank test, and binary logistic regression were used to analyze data. Results: (I) Baseline TMR could predict the IR to CIRT with a baseline TMR cut-off value of 2.35, an area under the curve (AUC) of 0.85 [95% confidence interval (CI): 0.62-1.00], a sensitivity of 80.0%, a specificity of 87.5%, and an accuracy of 85.7%. Taking the baseline TMR =2.35 as the cut-off value of high-hypoxia and low-hypoxia group, the IR rate of the high-hypoxia group [66.7% (4/6)] and the low-hypoxia group [6.7% (1/15)] was statistically different (P=0.01). (II) ΔTMR could predict early treatment response after CIRT at initial follow-up, with a cut-off value of ΔTMR =36.6%, AUC of 0.80 (95% CI: 0.61-1.00), sensitivity of 72.7%, specificity of 90.0% and accuracy of 71.4%. Conclusions: A higher degree of tumor hypoxia may be associated with a better IR to CIRT. ΔTMR could predict early treatment response after CIRT.

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Carbon ion beams have the unique property of higher linear energy transfer, which causes clustered damage of DNA, impacting the cell repair system. This sometimes triggers apoptosis and the release in the cytoplasm of damaged DNA, leading to type I interferon (IFN) secretion via the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway. Dendritic cells phagocytize dead cancer cells and damaged DNA derived from injured cancer cells, which together activate dendritic cells to present cancer-derived antigens to antigen-specific T cells in the lymph nodes. Thus, carbon ion radiation therapy (CIRT) activates anti-cancer immunity. However, cancer is protected by the tumor microenvironment (TME), which consists of pro-cancerous immune cells, such as regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. The TME is too robust to be destroyed by the CIRT-mediated anti-cancer immunity. Various modalities targeting regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages have been developed. Preclinical studies have shown that CIRT-mediated anti-cancer immunity exerts its effects in the presence of these modalities. In this review article, we provide an overview of CIRT-mediated anti-cancer immunity, with a particular focus on recently identified means of targeting the TME.

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Radioterapia de Iones Pesados , Células Supresoras de Origen Mieloide , Neoplasias , Humanos , Neoplasias/patología , Linfocitos T Reguladores , ADN , Microambiente Tumoral

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INTRODUCTION: Preserving the endocrine and reproductive function in young female cancer patients undergoing pelvic radiation is a significant challenge. While the photon beam radiation's adverse effects on the uterus and ovaries are well established, the impact of pelvic carbon ion radiotherapy on women's reproductive function is largely unexplored. Strategies such as oocyte cryopreservation and ovarian transposition are commonly recommended for safeguarding future fertility. METHODS: This study presents a pioneering case of successful pregnancy after carbon ion radiotherapy for locally advanced sacral chondrosarcoma. RESULTS: A multidisciplinary approach facilitated the displacement of ovaries and uterus before carbon ion radiotherapy, resulting in the preservation of endocrine and reproductive function. CONCLUSION: The patient achieved optimal oncological response and delivered a healthy infant following the completion of cancer treatment.

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Preservación de la Fertilidad , Radioterapia de Iones Pesados , Femenino , Humanos , Embarazo , Criopreservación/métodos , Fertilidad/fisiología , Preservación de la Fertilidad/métodos , Radioterapia de Iones Pesados/efectos adversos , Ovario , Adulto

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BACKGROUND AND PURPOSE: Particle therapy, mainly including carbon-ion radiotherapy (CIRT) and proton beam therapy (PBT), has dose distribution advantages compared to photon radiotherapy. It has been widely reported as a promising treatment method for early non-small cell lung cancer (NSCLC). However, its application in locally advanced non-small cell lung cancer (LA-NSCLC) is relatively rare, and its efficacy and safety are inconclusive. This study aimed to provide systematic evidence for evaluating the efficacy and safety of particle therapy for inoperable LA-NSCLC. METHODS: To retrieve published literature, a systematic search was conducted in PubMed, Web of Science, Embase, and Cochrane Library until September 4, 2022. The primary endpoints were local control (LC) rate, overall survival (OS) rate, and progression-free survival (PFS) rate at 2 and 5 years. The secondary endpoint was treatment-related toxicity. The pooled clinical outcomes and 95% confidence intervals (CIs) were calculated by using STATA 15.1. RESULTS: Nineteen eligible studies with a total sample size of 851 patients were included. The pooled data demonstrated that the OS, PFS, and LC rates at 2 years of LA-NSCLC treated by particle therapy were 61.3% (95% CI = 54.7-68.7%), 37.9% (95% CI = 33.8-42.6%) and 82.2% (95% CI = 78.7-85.9%), respectively. The pooled 5-year OS, PFS, and LC rates were 41.3% (95% CI = 27.1-63.1%), 25.3% (95% CI = 16.3-39.4%), and 61.5% (95% CI = 50.7-74.6%), respectively. Subgroup analysis stratified by treatment type showed that the concurrent chemoradiotherapy (CCRT, PBT combined with concurrent chemotherapy) group had better survival benefits than the PBT and CIRT groups. The incidence rates of grade 3/4 esophagitis, dermatitis, and pneumonia in LA-NSCLC patients after particle therapy were 2.6% (95% CI = 0.4-6.0%), 2.6% (95% CI = 0.5-5.7%) and 3.4% (95% CI = 1.4-6.0%), respectively. CONCLUSIONS: Particle therapy demonstrated promising efficacy and acceptable toxicity in LA-NSCLC patients.

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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia de Protones , Humanos , Supervivencia sin Progresión , Terapia de Protones/efectos adversos , Quimioradioterapia

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The feasibility and efficacy of particle beam therapy (PBT) using protons or carbon ions were compared with those of photon-based stereotactic body radiotherapy (SBRT) for primary renal cell carcinoma (RCC) via a systematic review and nationwide registry for PBT (Japanese Society for Radiation Oncology [JASTRO] particle therapy committee). Between July 2016 and May 2019, 20 patients with non-metastatic RCC who were treated at six Japanese institutes (using protons at three, using carbon ions at the other three) were registered in the nationwide database and followed up prospectively. The 20 patients comprised 15 men and had a median age of 67 (range: 57-88) years. The total radiation dose was 66-79.6 Gy (relative biological effectiveness [RBE]). Over a median follow up of 31 months, the 3-year rates of overall survival (OS) and local control (LC) were 100% and 94.4%, respectively. No grade ≥ 3 toxicities were observed. Based on a random effects model, a meta-analysis including the present results revealed 3-year OS rates after SBRT and PBT of 75.3% (95% CI: 57.3-86.6) and 94.3% (95% CI: 86.8-97.6), respectively (P = 0.005), but the difference in LC rates between the two methods was not observed (P = 0.63). PBT is expected to have similar if not better treatment results compared with SBRT for primary renal cancer. In particular, PBT was shown to be effective even for large RCC and could provide a therapeutic option when SBRT is not indicated.

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Carcinoma de Células Renales , Neoplasias Renales , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Carbono , Carcinoma de Células Renales/radioterapia , Carcinoma de Células Renales/secundario , Pueblos del Este de Asia , Neoplasias Renales/radioterapia , Protones , Sistema de Registros , Femenino

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Background: Heavy ion radiotherapy, such as carbon ion radiotherapy (CIRT), has multiple advantages over conventional photon therapy. Cisplatin, as a classic anti-tumor drugs, has been tested and discovered as a photon radiosensitizer in several cell lines, including head and neck squamous cell carcinoma (HNSCC). Hence, the aim of our study is to evaluate whether cisplatin can sensitize CIRT towards HNSCC cell lines in vitro. Methods: Human nasopharyngeal carcinoma cell line CNE-2, human tongue squamous carcinoma cell line TCA 8113 and human hypopharynx squamous carcinoma cell line FADU were all irradiated with photon beam of 2, 4, 6, 8 Gy (physical dose) and carbon ion beam of 1, 2, 3, 4 Gy (physical dose) and treated with cisplatin. Cell survival was assessed by clonogenic survival assay. Results: CIRT showed significantly stronger cytotoxic effect than standard photon radiotherapy. The relative biological effectiveness (RBE) of carbon ion beam at 10% survival ( R B E 10 ) was calculated 3.07 for CNE-2, 2.33 for TCA 8113 and 2.36 for FADU. Chemoradiotherapy (both photon radiotherapy and CIRT) was more effective than radiotherapy alone. In vitro sensitizer enhancement ratios (SERs) of cisplatin in CNE-2, TCA 8113 and FA DU cell lines after photon irradiation were 1.33, 1.14 and 1.21, while after carbon ion irradiation were 1.02, 1.00 and 0.96, showed that cisplatin sensitized photon irradiation but showed no sensitization effect in carbon ion irradiation in all tested cell lines. Conclusions: In conclusion, high linear energy transfer (LET) CIRT was more effective than photon irradiation to prevent the proliferation of HNSCC cell lines. Additional treatment with cisplatin could sensitize photon irradiation but showed no effect on carbon ion irradiation.

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Anti-cancer treatments for lung cancer patients with interstitial lung disease (ILD) are challenging. The treatment options for ILD are often limited because of concerns that treatments can cause acute exacerbation (AE) of ILD. This study aimed to analyze the outcomes of carbon-ion radiotherapy (CIRT) for stage I non-small cell lung cancer (NSCLC) with ILD, using a multi-institutional registry. Patients with ILD who received CIRT for stage I NSCLC in CIRT institutions in Japan were enrolled. The indication for CIRT was determined by an institutional multidisciplinary tumor board, and CIRT was performed in accordance with institutional protocols. Thirty patients were eligible. The median follow-up duration was 30.3 months (range, 2.5-58 months), and the total dose ranged from 50 Gy (relative biological effectiveness [RBE]) to 69.6 Gy (RBE), and five different patterns of fractionation were used. The beam delivery method was passive beam in 19 patients and scanning beam in 11 patients. The 3-year overall survival (OS), cause-specific survival, disease-free survival (DFS) and local control (LC) rates were 48.2%, 62.2%, 41.2% and 88.1%, respectively. Grade > 2 radiation pneumonitis occurred in one patient (3.3%). In conclusion, CIRT is a safe treatment modality for stage I NSCLC with concomitant ILD. CIRT is a safe and feasible treatment option for early lung cancer in ILD patients.

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Carcinoma de Pulmón de Células no Pequeñas , Radioterapia de Iones Pesados , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Humanos , Carbono , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Pueblos del Este de Asia , Pulmón/patología , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/radioterapia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/radioterapia

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Response evaluation of carbon-ion radiotherapy poses a diagnostic challenge. Due to its functional aspects, fluorodeoxyglucose positron emission tomography (FDG/PET) has a role in the diagnosis of photon radiation therapy. In addition, several studies suggested that FDG/PET may be useful to select the optimal site for performing a diagnostic biopsy. Here, we report a 73-year-old female in which FDG/PET was effective in determining the recurrence of liposarcoma and the therapeutic effect. Based on the results of FDG/PET, we could make a pathologic definitive diagnosis and selectively performing carbon-ion radiotherapy for active tumors.

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Objectives: To establish and validate a linear model utilizing diaphragm motion (DM) to predict the displacement of liver tumors (DLTs) for patients who underwent carbon ion radiotherapy (CIRT). A total of 60 pairs of planning and reviewing four-dimensional computed tomography (4DCT) sets over 23 patients were used. Method: We constructed an averaged computed tomography (CT) set for each either planning or reviewing 4DCT within respiratory phases between 20% of exhale and inhale. A rigid image registration to align bony structures was performed between planning and reviewing 4DCT. The position changes on top of diaphragm in superior-inferior (SI) direction between 2 CTs to present DM were obtained. The translational vectors in SI from matching to present DLT were obtained. The linear model was built by training data for 23 imaging pairs. A distance model utilized the cumulative probability distribution (CPD) of DM or DLT and was compared with the linear model. We conducted the statistical regression analysis with receiver operating characteristic (ROC) testing data of 37 imaging pairs to validate the performance of our linear model. Results: The DM within 0.5 mm was true positive (TP) with an area under the ROC curve (AUC) of 0.983 to predict DLT. The error of predicted DLT within half of its mean value indicated the reliability of prediction method. The 23 pairs of data showed (4.5 ± 3.3) mm for trend of DM and (2.2 ± 1.6) mm for DLT. A linear model of DLT = 0.46*DM + 0.12 was established. The predicted DLT was (2.2 ± 1.5) mm with a prediction error of (0.3 ± 0.3) mm. The accumulated probability of observed and predicted DLT with < 5.0 mm magnitude was 93.2% and 94.5%, respectively. Conclusion: We utilized the linear model to set the proper beam gating for predicting DLT within 5.0 mm to treat patients. We will investigate a proper process on x-ray fluoroscopy images to establish a reliable model predicting DLT for DM observed in x-ray fluoroscopy in the following two years.

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Radioterapia de Iones Pesados , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Diafragma/diagnóstico por imagen , Diafragma/patología , Reproducibilidad de los Resultados , Movimiento (Física) , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patología , Tomografía Computarizada Cuatridimensional/métodos , Respiración , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias Pulmonares/radioterapia

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Background: Although carbon-ion radiotherapy (CIRT) may improve outcome for patients with locoregionally recurrent nasopharyngeal carcinoma (LR-NPC), local progression still remains one of the major failure patterns. This suggests an unmet need of markers for predicting disease control after re-irradiation and potentially guiding tailored treatment. The purpose of this study was to explore the predictive value of pre-treatment 3'-deoxy-3'-[18F]fluorothymidine (FLT)-positron emission tomography (PET) for patients with locally advanced LR-NPC. Methods: In this retrospective analysis, LR-NPC patients with locally advanced stage (stage III/IV) who received pre-treatment FLT-PET between June, 2015, and August, 2017, were retrospective reviewed and included in this study. OS and local progression-free survival (LPFS) were calculated using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses of LPFS were performed. FLT-derived parameters, including SUVmax, metabolic tumor volume (MTV), and total lesion thymidine (TLT) were examined. The relationship between FLT-derived parameters and mucosal necrosis was tested by the Wilcoxon test. Results: A total of 27 patients with a median follow-up of 31.3 months were included in this analysis. The 2-year OS and LPFS rates were 85.2% and 47.9%, respectively. In multivariable analysis, except for TLT-40% (P=0.059), all pre-treatment MTVs (P=0.040 for MTV-40%; P=0.021 for MTV-50%; P=0.026 for MTV-60%) and TLTs (P=0.043 for TLT-50%; P=0.048 for TLT-60%) were significantly related to LPFS. Moreover, MTVs and TLTs with various boundaries (except for MTV-40%) were also associated with the development of mucosal necrosis after CIRT. Conclusions: In the current study, a significant association between pre-treatment FLT-PET and LPFS was observed in patients with locally advanced LR-NPC. Further investigations are warranted to confirm the predictive role of FLT-PET.

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Background: To investigate the maximal tolerated dose (MTD) of a carbon-ion radiotherapy (CIRT) boost prior to standard dose proton radiotherapy (PRT) for newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA) patients with residual lesion after resection. Methods: In total, 18 patients with high-grade glioma (HGG) (16 with GBM and 2 with AA) were enrolled in a prospective 3×3 design phase 1 trial. We investigated four dose-levels of CIRT boost [9 (starting level), 12, 15, and 18 Gy relative biological effectiveness (RBE)] delivered in three equal fractions prior to the standard dose PRT (60 Gy RBE in 30 fractions). Concurrent temozolomide (TMZ) was not provided during the CIRT boost but was initiated on the first day of PRT. Acute and late toxicities were scored based on the Common Terminology Criteria for Adverse Events (CTCAE, v 4.03). Dose-limiting toxicities (DLTs) were defined as radiation-induced severe toxicities (≥ grade 3). Results: With a median follow-up of 17.9 months, no severe (≥ grade 3) acute or late toxicities were observed in patients treated with the first three dose levels (CIRT boost doses of 9, 12, 15 Gy RBE). Severe late toxicity (grade 3 radiation necrosis) was observed in the first patient treated with the 18 Gy RBE CIRT boost level. Therefore, this trial was terminated and the MTD of the induction CIRT boost was determined at 15 Gy RBE in 3 fractions. At the time of this analysis, both patients with AA were alive without disease progression. The progression-free survival (PFS) and overall survival (OS) for GBM at 12 months were 50.6% and 78.6%, respectively. Conclusions: Particle beam radiotherapy consisting of a CIRT boost of 15 Gy RBE (in 3 fractions) following standard dose PRT (60 Gy RBE in 30 fractions), and used in conjunction with TMZ, is safe and potentially effective for patients with HGG.

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Background: Nasopharyngeal adenoid cystic carcinoma (NACC) is a distinct subgroup of adenoid cystic carcinoma (ACC) with limited surgical access but predilection of regional and distant metastasis. Although radiotherapy is an integral treatment for patients with NACC, photon-based radiotherapy yielded suboptimal local control. Because of its advantages in biology and physics properties, carbon-ion radiotherapy (CIRT) was attempted for the treatment of head and neck ACC; however, the use of CIRT specifically for NACC has not been investigated. Methods: Patients with NACC that received CIRT alone or a combination of CIRT and proton beam therapy (PBT) at the Shanghai Proton and Heavy Ion Center (SPHIC) between July 2016 and March 2019 were included in the analysis. Patients with newly diagnosed NACC received combined therapy of CIRT (as boost) and PBT, and those with recurrent disease received CIRT alone. Overall survival (OS), local progression-free survival (LPFS), regional progression-free survival (RPFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier method. Results: A total of 22 patients were included in this analysis. Among those, 18 patients had newly diagnosed NACC (17 with locally advanced disease), and 4 had recurrent NACC including 2 failed previous irradiation. After a median follow-up of 30.9 months, the 2-year OS rate, PFS rate, LPFS rate, RPFS rate and DMFS rate were 100%, 84.8%, 94.4%, 100%, and 84.8%, respectively. Three patients experienced grade 3 mucositis or xerostomia. No late toxicity of grade ≥3 was observed. Conclusions: CIRT alone or in combination with PBT appeared to be a promising modality for the treatment of NACC and produced satisfactory local disease control and toxicity profile. Distant metastasis remained to be a substantial mode for treatment failure. Further follow-up is necessary to evaluate long-term survivals and late toxicity profile.

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Background: Treatment of radiation-induced second primary malignancy (RI-SPM) is challenging and usually associated with poor outcomes. For patients with unresectable or incompletely resected diseases, carbon-ion radiotherapy (CIRT) offers physical and biologic advantages over photon-based re-irradiation. We report the results of salvage CIRT in 15 patients with RI-SPM. Methods: Fifteen consecutive and non-selected patients with RI-SPM who underwent salvage CIRT at the Shanghai Proton and Heavy Ion Center between November 2015 and May 2019 were included in this retrospective study. CIRT doses were 57.5-69 Gy (RBE) [at 2.5-3.0 Gy (RBE)/daily fraction]. The actuarial 1-year overall survival (OS), locoregional progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates as well as acute/late toxicities were analyzed. Results: Among the 15 patients included, 10 were soft tissue sarcomas, 2 were chondrosarcomas, 1 was osteosarcoma, 1 was squamous cell carcinoma and 1 was esthesioneuroblastoma. With a median follow-up of 13.0 (range, 2.73-29.63) months, the actuarial 1-year OS, LPFS, DMFS, and PFS rates were 69.3%, 53.0%, 92.9%, and 48.2%, respectively. No grade 2 and grade 3 acute adverse effect was observed. One patient experienced grade 4 hemorrhage which required embolization during CIRT, and lately died from hemorrhage (grade 5) at 3.4 months after the completion of CIRT. No other late adverse effects of ≥ grade 2 was observed. Conclusions: Salvage CIRT provided relatively safe and effective short-term outcome for patients with unresectable or in-completely resected RI-SPM, as compared to historical data on re-irradiation using the conventional photon beam technology. However, further improvement in both disease control and toxicity prevention is needed.

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Carbon-ion radiotherapy (CIRT) is an important part of modern radiotherapy. Compared to conventional photon radiotherapy modalities, CIRT brings two major types of advantages to physical and biological aspects respectively. The physical advantages include a substantial dose delivery to the tumoral area and a minimization of dose damage to the surrounding tissue. The biological advantages include an increase in double-strand breaks (DSBs) in DNA structures, an upturn in oxygen enhancement ratio and an improvement of radiosensitivity compared with X-ray radiotherapy. The two advantages of CIRT are that the therapy not only inflicts major cytotoxic lesions on tumor cells, but it also protects the surrounding tissue. According to annual diagnoses, lung cancer is the second most common cancer worldwide, followed by breast cancer. However, lung cancer is the leading cause of cancer death. Patients with stage I non-small cell lung cancer (NSCLC) who are optimally received the treatment of lobectomy. Some patients with comorbidities or combined cardiopulmonary insufficiency have been shown to be unable to tolerate the treatment when combined with surgery. Consequentially, radiotherapy may be the best treatment option for this patient category. Multiple radiotherapy options are available for these cases, such as stereotactic body radiotherapy (SBRT), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT). Although these treatments have brought some clinical benefits to some patients, the resulting adverse events (AEs), which include cardiotoxicity and radiation pneumonia, cannot be ignored. The damage and toxicity to normal tissue also limit the increase of tumor dose. Due to the significant physical and biological advantages brought by CIRT, some toxicity induced by radiotherapy may be avoided with CIRT Bragg Peak. CIRT brought clinical benefits to lung cancer patients, especially geriatric patients. This review introduced the clinical efficacy and research results for non-small cell lung cancer (NSCLC) with CIRT.

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From August 2019 to August 2020, we inserted polyglycolic acid (PGA) spacers and administered carbon ion radiotherapy (CIRT) to three cases of retroperitoneal sarcoma at our hospital. We aimed to investigate its utility and safety for retroperitoneal sarcoma. We analyzed changes in PGA spacer volume and corresponding computed tomography (CT) values in addition to the dose distribution using in-room CT images that were obtained during treatment. We assessed adverse events and investigated the suitability, safety and effectivity of PGA spacer insertion. During treatment, changes in PGA spacer volumes and CT values were confirmed. Volumes increased in patients with a folded PGA spacer, and it increased 1.6-fold by the end of irradiation compared with planning CT. The CT values decreased by 20-50 Hounsfield units at the end of irradiation compared to the planning CT. Dose distribution evaluation showed that the dose to the gastrointestinal tract adjacent to the tumor was maintained below the tolerable dose, and a sufficient dose was delivered to the target by PGA spacer insertion. One case of subileus caused during abdominal surgery for PGA spacer insertion occurred. No other adverse events, such as digestive disorders, were observed. CIRT with PGA spacer insertion for retroperitoneal sarcomas is safe and effective. For cases in which there is no option but to perform irradiation using a PGA spacer, precautionary measures such as verification of dose distributions using CT images are necessary.

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Radioterapia de Iones Pesados , Sarcoma , Neoplasias de los Tejidos Blandos , Implantes Absorbibles , Radioterapia de Iones Pesados/métodos , Humanos , Ácido Poliglicólico/uso terapéutico , Sarcoma/radioterapia , Sarcoma/cirugía

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Adenoid cystic carcinoma (ACC) is a rare, basaloid, epithelial tumor, arising mostly from salivary glands. Radiation therapy can be employed as a single modality for unresectable tumors, in an adjuvant setting after uncomplete resection, in case of high-risk pathological features, or for recurrent tumors. Due to ACC intrinsic radioresistance, high linear energy transfer (LET) radiotherapy techniques have been evaluated for ACC irradiation: while fast neutron therapy has now been abandoned due to toxicity concerns, charged particle beams such as protons and carbon ions are at present the beams used for hadron therapy. Carbon ion radiation therapy (CIRT) is currently increasingly used for ACC irradiation. The aim of this review is to describe the immunological, molecular and clinicopathological bases that support ACC treatment with CIRT, as well as to expose the current clinical evidence that reveal the advantages of using CIRT for treating ACC.

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Rectum and bladder volumes play an important role in the dose distribution reproducibility in prostate cancer adenocarcinoma (PCa) radiotherapy, especially for particle therapy, where density variation can strongly affect the dose distribution. We investigated the reliability and reproducibility of our image-guided radiotherapy (IGRT) and treatment planning protocol for carbon ion radiotherapy (CIRT) within the phase II mixed beam study (AIRC IG 14300) for the treatment of high-risk PCa. In order to calculate the daily dose distribution, a set of synthetic computed tomography (sCT) images was generated from the cone beam computed tomography (CBCT) images acquired in each treatment session. Planning target volume (PTV) together with rectum and bladder volume variation was evaluated with sCT dose-volume histogram (DVH) metric deviations from the planning values. The correlations between the bladder and rectum volumes, and the corresponding DVH metrics, were also assessed. No significant difference in the bladder, rectum, and PTV median volumes between the planning computed tomography (pCT) and the sCT was found. In addition, no significant difference was assessed when comparing the average DVHs and median DVH metrics between pCT and sCT. Dose deviations determined by bladder and rectum filling variations demonstrated that dose distributions were reproducible in terms of both target coverage and organs at risk (OARs) sparing.

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Until recently, radiation effects have been considered to be mainly due to nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures to ionizing radiation (IR) highly depend on activation and regulation through other molecular components of organelles that determine cell survival and proliferation capacities. As typical epigenetic-regulated organelles and central power stations of cells, mitochondria play an important pivotal role in those responses. They direct cellular metabolism, energy supply and homeostasis as well as radiation-induced signaling, cell death, and immunological responses. This review is focused on how energy, dose and quality of IR affect mitochondria-dependent epigenetic and functional control at the cellular and tissue level. Low-dose radiation effects on mitochondria appear to be associated with epigenetic and non-targeted effects involved in genomic instability and adaptive responses, whereas high-dose radiation effects (>1 Gy) concern therapeutic effects of radiation and long-term outcomes involving mitochondria-mediated innate and adaptive immune responses. Both effects depend on radiation quality. For example, the increased efficacy of high linear energy transfer particle radiotherapy, e.g., C-ion radiotherapy, relies on the reduction of anastasis, enhanced mitochondria-mediated apoptosis and immunogenic (antitumor) responses.

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Epigénesis Genética/efectos de la radiación , Mitocondrias/metabolismo , Radiación Ionizante , Transducción de Señal/efectos de la radiación , Transición Epitelial-Mesenquimal/efectos de la radiación , Inestabilidad Genómica/efectos de la radiación , Humanos , Mitocondrias/genética , Mitocondrias/efectos de la radiación , Dinámicas Mitocondriales/efectos de la radiación , Estrés Oxidativo/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

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

Asunto(s)

Radioterapia de Iones Pesados , Fantasmas de Imagen , Tejido Adiposo , Aire , Algoritmos , Huesos , Simulación por Computador , Humanos , Pulmón , Método de Montecarlo , Músculo Esquelético , Estudios Retrospectivos , Diente