Particle beam therapy for pelvic recurrence of colorectal cancer: a registry data analysis in Japan and a systematic review.

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

MRI Grading Scale Predicts Ambulatory Function After Radiotherapy for Metastatic Spinal Cord Compression: A Prospective Single-Institution Observational Study.

INTRODUCTION: Although magnetic resonance imaging (MRI) is an important modality for the diagnosis of metastatic spinal cord compression (MSCC), there are only a few reports on MSCC findings and symptoms after radiotherapy. We aimed to reveal the factors related to ambulatory function after treatment, including the MRI findings, in a prospective observational study. METHODS: Patients with suspected MSCC who were treated with radiotherapy were included in this study. Orthopedic surgeons evaluated the neurological function according to the Frankel grade. All patients underwent spinal MRI, and the degree of spinal cord compression was assessed by a radiologist and a radiation oncologist using an MRI grading scale. One month after treatment, orthopedic surgeons reassessed the Frankel grade. Twenty-three patients who were evaluated 1 month after radiotherapy were included in the analysis. RESULTS: Before radiotherapy, 17 patients were ambulatory and six were unable to walk. Furthermore, 13 patients were diagnosed with grade 3 compression on MRI (spinal cord compression with no cerebrospinal fluid seen on axial T2-weighted imaging). Patients with grade 3 MSCC were significantly more likely to be non-ambulatory at 1 month. CONCLUSIONS: The MRI grading scale for MSCC may be a prognostic factor for ambulatory function after radiotherapy. MRI findings could aid in determining the indication for radiotherapy.

Emerging Role of Carbon Ion Radiotherapy in Reirradiation of Recurrent Head and Neck Cancers: What Have We Achieved So Far?

Administering reirradiation for the treatment of recurrent head and neck cancers is extremely challenging. These tumors are hypoxic and radioresistant and require escalated radiation doses for adequate control. The obstacle to delivering this escalated dose of radiation to the target is its proximity to critical organs at risk (OARs) and possible development of consequent severe late toxicities. With the emergence of highly sophisticated technologies, intensity-modulated radiotherapy (IMRT) and stereotactic body radiotherapy have shown promising outcomes. Proton beam radiotherapy has been used for locally recurrent head and neck cancers because of its excellent physical dose distribution, exploring sharp Bragg peak properties with negligible entrance and exit doses. To further improve these results, carbon ion radiotherapy (CIRT) has been explored in several countries across Europe and Asia because of its favorable physical properties with minimal entrance and exit doses, sharper lateral penumbra, and much higher and variable relative biological efficacy, which cannot be currently achieved with any other form of radiation. Few studies have described the role of CIRT in recurrent head and neck cancers. In this article, we have discussed the different aspects of carbon ions in reirradiation of recurrent head and neck cancers, including European and Asian experiences, different dose schedules, dose constraints of OARs, outcomes, and toxicities, and a brief comparison with proton beam radiotherapy and IMRT.

Implementation rate and effects of multidisciplinary team meetings on decision making about radiotherapy: an observational study at a single Japanese institution.

BACKGROUND: Cancer treatment requires a multidisciplinary approach. Therefore, multidisciplinary team meetings (MDTMs) have been widely used to determine the direction of treatment. However, no standard provisions exist for conducting MDTMs, and recommendations discussed in MDTMs are sometimes not implemented. ​This study analyzed the indications for radiotherapy discussed and recommended at MDTMs, identified the rate of radiotherapy recommendations for patients that were not implemented, and clarified the reasons at a single academic center in Japan. METHODS: This was a cross-sectional study that analyzed the minutes and electronic medical records of cases discussed at MDTMs held between April 2012-March 2017 at Yamagata University Hospital. We categorized how radiotherapy was initially presented at MDTMs, determined the rate of radiotherapy recommendations made through MDTMs, analyzed whether treatment recommendations were subsequently implemented, and examined the causes of non-implementation. We performed a statistical analysis to assess some clinical factors (sex, age, number of multidisciplinary team meetings, and classification of planned treatment) associated with the non-implementation of radiotherapy recommendations from MDTMs. RESULTS: A total of 1813 cases were discussed at MDTMs, of which 71% (1293 cases) were presented with treatment plans, including radiotherapy. Further, 66% (1205 cases) were recommended for radiotherapy through the MDTMs. Recommendations from MDTMs were not implemented in 7% (142 cases). The most typical reason for non-implementation was the clinician's opinion (30%), followed by patient preferences (27%) and disease progression (20%). Change in cancer stage and improvement in symptoms were 12% and 4%, respectively. These ratios were similar each year. We could not find the factors associated with the non-implementation of radiotherapy recommendations from MDTMs. CONCLUSIONS: MDTMs had a significant effect on the recommendation of radiotherapy for each patient with a tumor. The primary reason for the non-implementation of decisions made at MDTMs was the opinion of clinicians and the patient's preference. These results were similar to previous studies. We need to establish a monitoring system where patients themselves can decide the treatments based on their choices while using the recommendations from MDTMs.

Prediction of the minimum spacer thickness required for definitive radiotherapy with carbon ions and photons for pelvic tumors: an in silico planning study using virtual spacers.

We aimed to predict the minimum distance between a tumor and the gastrointestinal (GI) tract that can satisfy the dose constraint by creating simulation plans with carbon-ion (C-ion) radiotherapy (RT) and photon RT for each case assuming insertion of virtual spacers of various thicknesses. We enrolled 55 patients with a pelvic tumor adjacent to the GI tract. Virtual spacers were defined as the overlap volume between the GI tract and the volume expanded 7-17 mm from the gross tumor volume (GTV). Simulation plans (70 Gy in 35 fractions for at least 95% of the planning target volume [PTV]) were created with the lowest possible dose to the GI tract under conditions that meet the dose constraints of the PTV. We defined the minimum thickness of virtual spacers meeting D2 cc of the GI tract <50 Gy as 'MTS'. Multiple regression was used with explanatory variables to develop a model to predict MTS. We discovered that MTSs were at most 9 mm and 13 mm for C-ion RT and photon RT plans, respectively. The volume of overlap between the GI tract and a virtual spacer of 14 mm in thickness (OV14)-PTV was found to be the most important explanatory variable in the MTS prediction equation for both C-ion and photon RT plans. Multiple R2 values for the regression model were 0.571 and 0.347 for C-ion RT and photon RT plans, respectively. In conclusion, regression equations were developed to predict MTS in C-ion RT and photon RT.

Efficacy and feasibility of re-irradiation using carbon ions for pancreatic cancer that recurs after carbon-ion radiotherapy.

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

Nationwide survey of radiation therapy in Japan for lung cancer complicated with interstitial lung disease.

The purpose of this study was to clarify the opinions of radiation oncologists in Japan regarding treatment for lung cancer complicated with interstitial lung disease (ILD) by a questionnaire survey, and the risk of acute exacerbation (AE) after radiotherapy. Questionnaires were sent to all of the facilities in which radiation therapy is performed for lung cancer in Japan by using the mailing list of the Japanese Society for Radiation Oncology (JASTRO). The questionnaire survey was conducted to clarify who judges the existence of ILD, the indications for radiation therapy in cases of ILD-combined lung cancer, and the ratio of ILD-combined lung cancer in lung cancer patients treated with radiation therapy. Patients with ILD-combined lung cancer who received radiotherapy during the period from April 2014 to March 2015 were retrospectively analysed. Any cases of AE without any other obvious cause were included. ILD confirmation was performed by central radiologists using computed tomography images. A total of 47 facilities responded to the questionnaire. Radiation therapy was an option in cases of ILD-combined lung cancer in 39 (83%) of the facilities. The indication for radiation therapy was based on image findings in 35 (90%) of the 39 facilities in which radiation therapy was acceptable or was a choice in some cases of ILD. The final indication was based on the opinion of the pulmonologist in 29 (74%) of those 39 facilities. In fiscal year 2014, a total of 2128 patients in 38 facilities received chest irradiation. Seventy-eight (3.7%) of those 2128 patients had ILD-combined lung cancer. Sixty-seven patients were included in patient analysis. AE occurred in 5 patients (7.5%), and one of those 5 patients (20.0%) died from radiation-induced AE. The median period from radiotherapy to AE was 4 months (range, 2-7 months). The following four independent risk factors for AE were identified in univariate analysis: non-advanced age (<75 years), increased C-reactive protein level (≥0.3 mg/dl), adjuvant chemotherapy and ≥ Grade 2 radiation pneumonitis. Radiotherapy was an option for lung cancer even in cases with ILD in 83% (39/47) of the facilities in Japan. Seventy-eight (3.7%) of 2128 patients who received radiation therapy for lung cancer had ILD. Radiotherapy for ILD-combined lung cancer may induce AE at a substantial rate and AE can be life-threatening. Minimizing the risk of radiation pneumonitis might enable the risk of AE to be reduced.

Long-term outcomes of skull base chordoma treated with high-dose carbon-ion radiotherapy.

BACKGROUND: We evaluated the long-term efficacy and safety of carbon-ion radiotherapy (C-ion RT) for skull base chordoma, a rare neoplasm. METHODS: Thirty-four patients with skull base chordoma who were treated with C-ion RT were prospectively enrolled and analyzed retrospectively. C-ion RT was delivered with 60.8 Gy (relative biological effectiveness [RBE]) in 16 fractions at four fractions per week. RESULTS: The median follow-up period was 108 months. The 5- and 9-year local control rates were 76.9% and 69.2%, respectively. The 5- and 9-year overall survival rates were 93.5% and 77.4%, respectively. Regarding grade 3 or more severe late reactions, one patient developed a grade 3 mucosal ulcer, two developed grade 4 ipsilateral optic nerve injuries, and one developed a grade 5 mucosal ulcer at 9 years and 3 months after C-ion RT. CONCLUSION: C-ion RT with 60.8 Gy (RBE)/16 fractions is a promising treatment option for inoperable skull base chordoma.

Long-term outcomes and toxicities of carbon-ion radiotherapy in malignant tumors of the sphenoid sinus.

BACKGROUND: Most of the primary sphenoid sinus tumors present with locally advanced stages with involvement of adjacent critical structures and are not amenable to radical resection. We sought to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for sphenoid sinus malignancies. METHODS: This is a retrospective analysis of 22 patients of primary sphenoid carcinomas treated with definitive C-ion RT. RESULTS: Adenoid cystic carcinoma was the most common histology (15 patients, 68.2%). The median follow-up of this cohort was 48.5 months. The actuarial local control and overall survival at 5 years were 51.0% and 62.7%, respectively. Grade 4 visual impairment and grade 4 brain necrosis were seen in six and one patient, respectively. CONCLUSION: C-ion RT can provide a reasonably good clinical outcome in locally advanced sphenoid sinus malignancies with a marginally higher late toxicity profile because of extremely close proximity of the target volume to critical structures.

Assessment of risk factors associated with development of oronasal fistula as a late complication after carbon-ion radiotherapy for head and neck cancer.

BACKGROUND: Oronasal fistulae (ONF) are one of the rare but serious complications of conventional photon radiotherapy. This study aimed to identify the risk factors for the development of ONF after carbon-ion radiotherapy (C-ion RT). MATERIALS AND METHODS: The data of 62 cases of sinonasal and oral cavity cancers treated with C-ion RT and followed-up in excess of 5 years were retrospectively reviewed. The correlation between the clinical and dosimetric parameters and the development of ONF was analysed. RESULTS: A total of 80.6% cases had sinonasal malignancies, and most tumours had advanced T stages (96.8%). Maxillary invasion was observed in 16 cases (25.8%), and malignant melanoma was the most common histology (46.8 %). All the cases received a dose of between 57.6 Gy (RBE) and 64 Gy (RBE) in 16 fractions over 4 weeks. At a median follow up of 88.8 months, 23 cases (37.1%) developed small localised ONF; however, none were of grade III severity. On separate multivariate analyses of clinical parameters in the entire cohort and in cases without maxillary invasion, the number of teeth irradiated with more than 50 Gy (RBE) was found to be the common significant independent risk factor for development of ONF. CONCLUSION: The number of teeth irradiated with more than 50 Gy (RBE) is a significant independent risk factor for the development of ONF, which is a late complication of C-ion RT delivered in 16 fractions.

Influence of dose-averaged linear energy transfer on tumour control after carbon-ion radiation therapy for pancreatic cancer.

BACKGROUND AND PURPOSE: High linear energy transfer (LET) radiation carbon-ion radiotherapy (C-ion RT) is one of the most promising modalities for treating unresectable primary pancreatic cancers. However, how LET contributes to a therapeutic effect is not clear. To assess whether there is an enhanced effect of high LET radiation on tumour control, we aimed to determine the impact of dose-averaged LET on local control (LC) of primary pancreatic tumours. MATERIALS AND METHODS: A retrospective analysis of 18 patients with primary pancreatic carcinomas treated with definitive C-ion RT with concurrent chemotherapy in 2013 was conducted. The dose of irradiation was 55.2 Gy (RBE). The relationship between dose-averaged LET and LC of primary tumours was evaluated. RESULTS: All patients had histologically confirmed adenocarcinoma. The median follow-up duration was 22 months. The actuarial LC and overall survival (OS) at 18 months were 62.5% and 70.1%, respectively. There were no cases of grade ≥3 late toxicities observed. Local recurrences developed in four patients (22%), all of which were infield central recurrences. Although there were no significant differences in gross tumour volume (GTV) dose coverage, patients with higher minimum dose-averaged LET (LETmin) values within the GTV had better LC (dose-averaged LETmin ≥44 keV/microm; 18-months LC 100.0% vs 34.3%; p = 0.0366). CONCLUSION: Dose-averaged LETmin within the GTV was significantly associated with LC of primary pancreatic cancers. Our data suggest that outcomes for patients with unresectable primary pancreatic cancers receiving C-ion RT can be improved by modulating the dose-averaged LET within the GTV.

First prospective feasibility study of carbon-ion radiotherapy using compact superconducting rotating gantry.

OBJECTIVE: We had developed compact rotating gantry for carbon ion using superconducting magnets in 2015 which became clinically operational in 2017. The objective of this study was to assess the clinical feasibility and safety of using compact rotating gantry with three-dimensional active scanning in delivery of carbon-ion radiotherapy (C-ion RT) for relatively stationary tumours. METHODS: A prospective feasibility study was conducted with 10 patients who had been treated with C-ion RT using compact rotating gantry between April 2017 and April 2018 at Hospital of the National Institute of Radiological Sciences (NIRS) for head and neck and prostate cancers. The primary end point was evaluation of acute toxicities within 3 months of starting C-ion RT. RESULTS: Out of 10 cases 8 were of head and neck cancers and 2 were of prostate cancers. All of those eight head and neck cases were of locally advanced stages. Both of the prostate cancer patients belong to intermediate risk categories. None of the patients developed even Grade 2 or more severe skin reactions. Six out of eight cases with head and neck cancers experienced Grade 2 mucosal reactions; however, nobody developed Grade 3 or more severe mucosal reactions. There was no gastrointestinal reaction observed in prostate cancer patients. One patient developed Grade 2 genitourinary reaction. CONCLUSION: C-ion RT using compact rotating gantry and three-dimensional active scanning is a safe and feasible treatment for relatively less mobile tumours. ADVANCES IN KNOWLEDGE: This study will be the first step to establish the use of superconducting rotating gantry in C-ionRT in clinical setting paving the way for treating large number of patients and make it a standard of practice in the future.

Feasibility of Re-irradiation using carbon ions for recurrent head and neck malignancies after carbon-ion radiotherapy.

BACKGROUND AND PURPOSE: Locoregional recurrence after carbon-ion radiotherapy (CIRT) for primary head and neck malignancies, such as malignant mucosal melanoma, adenoid cystic carcinoma, and sarcoma, occurs occasionally. However, the treatment options are limited. We report on the toxicity and efficacy of re-irradiation using carbon ions for recurrent head and neck malignancies after CIRT. MATERIALS AND METHODS: Data of 48 patients with recurrent head and neck malignancies treated with re-irradiation with CIRT at our institution (2007-2016) were retrospectively analyzed. Twenty-one patients (43.8%) had malignant mucosal melanoma, 17 (35.4%) had adenoid cystic carcinoma, six (12.5%) had bone and soft tissue sarcomas, and four patients (8.3%) had other disease types. Tumor recurrences at re-irradiation were located in the paranasal cavity (n = 18, 37.5%), nasal cavity (n = 9, 18.8%), nasopharynx (n = 4, 8.3%), orbit (n = 3, 6.3%), cavernous sinus (n = 3, 6.3%), and at other sites (n = 11, 22.9%). The median dose of initial CIRT and that at re-irradiation were 57.6 Gy and 54.0 Gy (relative biological effectiveness [RBE]), respectively. None of the patients received concurrent chemotherapy. RESULTS: The median follow-up period after re-irradiation was 27.1 months. Five patients (10.4%) developed Grade 3 acute toxicities and 18 (37.5%) developed Grade ≥3 late toxicities, including Grade 5 central nervous system necrosis in one patient. The 2-year local control, locoregional control, progression-free survival, and overall survival rates were 40.5, 33.5%, 29.4%, and 59.6%, respectively. CONCLUSION: Re-irradiation using carbon ions may be a reasonable treatment option with tolerable toxicity for patients with recurrent head and neck malignancies after CIRT.

Radiotherapy for mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum: a case report.

Extra-nodal mucosa-associated lymphoid tissue (MALT) lymphoma is frequently involved with the upper gastrointestinal tract, but rarely involved with the rectum. We report a case of rectal MALT lymphoma treated by radiotherapy (RT) alone. A 74-year-old woman with lower abdominal pain was diagnosed with MALT lymphoma by endoscopic mucosal resection (EMR). She was diagnosed as stage IE (Ann Arbor) MALT lymphoma by diagnostic work-up and review of EMR specimens. Definitive RT was performed with curative intent, totaling 30 Gy in 15 fractions. Complete response was confirmed by colonoscopy after RT with no progression observed at 5 years. Definitive RT is effective for rectal MALT lymphoma.

Modified simultaneous integrated boost radiotherapy for large retroperitoneal malignant tumor: A case report.

The current study reports the case of a large retroperitoneal tumor treated with modified simultaneous integrated boost (SIB) radiotherapy. A 45-year-old female presented to the emergency department complaining of left abdominal pain and fever. A computed tomography scan detected a retroperitoneal tumor of 12×16×16 cm, and a biopsy revealed a poorly-differentiated adenocarcinoma. The patient was diagnosed with a large adenocarcinoma originating from the left ureter, with no distant metastasis. Due to the patient's poor physical condition, surgery was not recommended, and the patient was referred to the Department of Radiation Oncology (Yamagata University Hospital, Yamagata, Japan). Modified SIB radiotherapy was administered following the acquisition of written consent from the patient. The total irradiation dose to the center of the tumor and to the surrounding healthy tissue was ∼96 Gy/33 fractions and <60 Gy/33 fractions, respectively. At the end of the radiotherapeutic course, the tumor volume was reduced by ≥80%, and the residual tumor was surgically resected. As a result of the resection, a complete pathological response was confirmed; the patient has been recurrence-free for >3 years with no complications. Modified SIB radiotherapy may be safely administered, with favorable outcomes. Complete recovery can be achieved with this technique, even in a patient with a large radioresistant tumor.

Modified simultaneous integrated boost radiotherapy for unresectable locally advanced breast cancer: preliminary results of a prospective clinical trial.

BACKGROUND: The purpose of this study was to evaluate the effect of modified simultaneous integrated boost (SIB) radiotherapy for patients with extensive breast cancer. PATIENTS AND METHODS: Patients with macroscopic tumor and histologically proven adenocarcinoma of the breast were enrolled in the study. Patients were included whether they had or did not have previous surgery, chemotherapy, hormone therapy, or molecular targeted therapy; patients with past history of thoracic radiotherapy were excluded. Under conditions of not exceeding the tolerance dose for normal tissue, irradiation to the tumor was increased to the maximum possible extent using the modified SIB technique. RESULTS: Three breast cancer patients were treated with the modified SIB technique. All patients were diagnosed as T4b (median maximum diameter of the tumor: 16 cm; range, 15.5-22 cm), and all patients exhibited symptoms because of the extremely large tumor. The median total dose to the part of tumor tissue was 128.8 Gy (range, 110-140 Gy). Total dose to normal tissue was < 72 Gy in all patients. Although large tumors were radio-resistant, it was macroscopically confirmed that all tumors eventually disappeared. Although skin defects persisted because of tumor disappearance, there were no Grade ≥ 3 toxicities due to radiotherapy. CONCLUSION: Although much care is required in delivering extremely high doses of radiotherapy to the tumor, modified SIB radiotherapy was shown to be effective against extremely large tumors that could not be controlled using conventional radiotherapy. In future, an increase in the number of study patients and establishment of the technique will be required.

Relationship between serum reactive oxidative metabolite level and skin reaction in an irradiated rat model.

PURPOSE: Ionizing radiation generates free radicals and reactive oxygen species that induce DNA damage in vivo. This study aimed to determine the relationship between serum reactive oxygen metabolite (ROM) levels and skin reaction after irradiation in a rat model. METHODS AND MATERIALS: I. Female Wistar rats were classified into 0 Gy (control), 2 Gy, and 30 Gy groups; serum ROM levels were measured in the very acute phase. II. Other female Wistar rats were classified into 0 Gy (control), 30 Gy, 50 Gy, and 70 Gy groups; serum ROM levels were measured before and 3, 7, 16, 24, 31, and 38 days after irradiation. Skin reaction was evaluated according to the SRS (0-5) twice every week. RESULTS: Serum ROM levels in the subacute phase were significantly higher in the 50 and 70 Gy groups than in the 0 and 30 Gy groups [p = 0.029, repeated-measure analysis of variance (ANOVA)]. As expected, SRSs increased in the order of the 0 Gy, 30 Gy, 50 Gy, and 70 Gy groups and differed significantly among these groups (p < 0.001, repeated-measure ANOVA). Peak serum ROM levels were observed 16 days after irradiation in all irradiated groups and corresponded with the appearance of visible skin reaction after irradiation. CONCLUSIONS: Serum ROM levels may be useful for evaluating radiation damage in mammals. Further investigations are required to investigate changes in intracellular metabolism after irradiation at gene and protein levels.