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Systemic chemotherapy has significantly improved in recent years. In this study. the clinical impact of carbon-ion radiotherapy (CIRT) with concurrent chemotherapy for locally advanced unresectable pancreatic cancer (URPC) was evaluated. Methods: Patients with URPC who were treated with CIRT between January 2016 and December 2020 were prospectively registered and analyzed. The major criteria for registration were (1) diagnosed as URPC on imaging; (2) pathologically diagnosed adenocarcinoma; (3) no distant metastasis; (4) Eastern Cooperative Oncology Group performance status of 0–2; (5) tumors without gastrointestinal tract invasion; and (6) available for concurrent chemotherapy. Patients who received neoadjuvant chemotherapy (NAC) for more than one year prior to CIRT were excluded. Results: Forty-four patients met the inclusion criteria, and thirty-seven received NAC before CIRT. The median follow-up period of living patients was 26.0 (6.0–68.6) months after CIRT. The estimated two-year overall survival, local control, and progression-free survival rates after CIRT were 56.6%, 76.1%, and 29.0%, respectively. The median survival time of all patients was 29.6 months after CIRT and 34.5 months after the initial NAC. Conclusion: CIRT showed survival benefits for URPC even in the multiagent chemotherapy era.

Background The efficacy of first-line chemoradiotherapy for overall survival (OS) might be confounded by the subsequent treatments in patients with locally advanced non-small cell lung cancer (NSCLC). In this study, we assessed the associations of progression-free survival (PFS) and post-progression survival (PPS) with OS after chemoradiotherapy for locally advanced NSCLC using patient-level data. Patients and methods Between January 2011 and December 2018, 45 patients with locally advanced NSCLC who had received first-line chemoradiotherapy and in whom recurrence occurred were analysed. The associations of PFS and PPS with OS were analysed at the individual level. Results Linear regression and Spearman rank correlation analyses revealed that PPS was strongly correlated with OS (r = 0.72, p < 0.05, R2 = 0.54), whereas PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.34). The Glasgow prognostic score and liver metastases at recurrence were significantly associated with PPS (p < 0.001). Conclusions The current analysis of individual-level data of patients treated with first-line chemoradiotherapy implied that PPS had a higher impact on OS than PFS in patients with locally advanced NSCLC. Additionally, current perceptions indicate that treatment beyond progression after first-line chemoradiotherapy might strongly affect OS.

Background/Aim: Previous evaluation of the safety and clinical efficacy of re-irradiation for pelvic recurrence of rectal cancer after preoperative chemoradiotherapy (PCRT) and rectal surgery is insufficient. We evaluated the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for pelvic recurrence of rectal cancer after PCRT. Patients and Methods: We reviewed the medical records of patients treated with C-ion RT between August 2011 and December 2021 and analyzed the data of seven consecutive patients. The probabilities of overall survival (OS), local control (LC), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Toxicities were classified using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 4.0). Results: The median follow-up duration after C-ion RT initiation was 30.9 months. Five patients received 73.6 Gy [relative biological effectiveness (RBE)] in 16 fractions, and two patients received 57.6 Gy (RBE) in 12 fractions. All patients completed C-ion RT as scheduled. Two-year estimated OS, LC, and PFS rates after C-ion RT initiation were 100%, 83.3%, and 28.6%, respectively. No patients developed grade ≥3 acute toxicity. Regarding late toxicities, one patient who received Gore-Tex sheets as a spacer before C-ion RT developed grade 3 colon perforation, and then developed a grade 3 urinary tract disorder. One patient developed grade 2 peripheral neuropathy. Conclusion: C-Ion RT showed favorable local efficacy with minimal toxicity. C-Ion RT might be an effective treatment option for pelvic recurrence of rectal cancer after PCRT even when re-irradiation of the pelvis is required.

The promising results of the PACIFIC study led to the approval of consolidation durvalumab for coverage by the National Health Insurance (NHI) in 2018 for patients with locally-advanced unresectable non-small cell lung carcinoma (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT). However, the effect of NHI coverage on the patterns of care for this population remains unclear. Here, we conducted a questionnaire-based survey to determine the patterns of care for patients with stage II-III NSCLC treated with definitive radiotherapy in 2017 (pre-durvalumab era) or in 2019 (post-durvalumab era). Data were obtained from 11 radiotherapy facilities in Gunma prefecture, which has a population of 1.94 million. We identified 80 and 83 patients with stage II-III NSCLC who received definitive radiotherapy in Gunma in 2017 and 2019, respectively. At a given facility, CCRT was the treatment of choice in a significantly greater proportion of patients in 2019 than in 2017 (66% ± 20% vs 51% ± 29%, P = 0.041). Intensity-modulated radiotherapy (IMRT) was more frequent in 2019 than in 2017 (24% vs 1.2%). Carboplatin plus paclitaxel was used for CCRT at higher rate in 2019 than in 2017 (73% vs 44%). Consolidation durvalumab was performed in 73% (40/55) of CCRT-treated patients in 2019, and the treatment was performed for the planned 12 months in 45% (18/40) of patients. These data indicate that NHI coverage of durvalumab might be a possible reason for choosing CCRT in patients with stage II-III NSCLC in the real-world setting.

Little information is available on the risk factors for nasolacrimal duct obstruction after radiotherapy for head and neck tumors. We investigated the incidence and predictive dosimetric parameters for nasolacrimal duct obstruction following carbon-ion radiotherapy for head and neck tumors.Twenty-eight patients with head and neck non-squamous cell carcinoma were analyzed in this single-institution prospective study. More than half of the tumors were located in the nasal cavity and maxillary sinus. Carbon-ion radiotherapy consisting of 57.6 or 64.0 Gy(relative biological effectiveness; RBE) in 16 fractions was administered. Nasolacrimal duct obstruction was recorded according to Common Terminology Criteria for Adverse Events version 4.0. Cutoff values were determined using receiver operating characteristic (ROC) curve analysis. VX indicates the volume irradiated with X Gy(RBE).The median follow-up period was 60.3 months. Incidences of Grade 1 and 2 nasolacrimal duct obstructions were 46% (13/28) and 7% (2/28), respectively; no Grade 3 or greater toxicities were recorded. Throughout the dose range, the volumes of the irradiated nasolacrimal ducts were significantly higher in the obstruction-positive patients than in the obstruction-negative patients (p 0.001 for V10, V20, V30, V40, V50, and V60). Cutoff values determined by the ROC curve analysis classified the obstruction-positive patients with an accuracy of96% over the entire range of V10-V60.The incidence and predictive dosimetric parameters for nasolacrimal duct obstruction after carbon-ion radiotherapy were demonstrated in a prospective cohort. These data should help optimize carbon-ion radiotherapy treatments for patients with head and neck tumors.

Three-dimensional image-guided brachytherapy (3D-IGBT) has become the standard therapy for patients with cervical cancer. However, in this population, the impact of 3D-IGBT in elderly individuals remains unknown. This study assessed the efficacy of 3D-IGBT for elderly patients with cervical cancer.

The synthesis of optically active secondary and tertiary propargylic alcohols was accomplished by addition of lithium acetylide to chiral β-sulfinyl enones. Only a stoichiometric amount of the lithium acetylide was required and various substituents were tolerated. This reaction could be applied to substrates consisting of both ketones and aldehydes in high yields and excellent diastereoselectivities.

Background and Objective: Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitizing epidermal growth factor receptor (EGFR) mutations show a good response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). The subsequent treatments influence the evaluability of the efficacy of front-line therapy on overall survival (OS). Consequently, we evaluated the associations of relapse-free survival (RFS) and post-progression survival (PPS) with OS in patients who exhibited postoperative relapse of EGFR-mutated NSCLC. Materials and Methods: We analyzed the data of 35 patients with EGFR-mutated NSCLC who underwent complete resection between January 2007 and June 2019. The correlations of RFS and PPS with OS were evaluated at the individual patient level. Results: Linear regression and Spearman’s rank correlation analyses demonstrated that the PPS highly correlated with OS (r = 0.91, p &lt, 0.05, R2 = 0.85), whereas the RFS weakly associated with OS (r = 0.36, p &lt, 0.05, R2 = 0.25). Age and performance status at relapse were significantly associated with PPS. Conclusion: Overall, PPS was more strongly and significantly associated with OS than RFS. These results suggest that the OS of our cohort may be affected by treatments, besides postoperative relapse. However, larger-scale prospective studies are needed to confirm these results.

Background Adenoid cystic carcinoma (ACC) is a rare malignant tumor involving mostly the head and neck region, and frequently the salivary glands. The development of lung metastasis after treatment of the primary tumor is a common occurrence in ACC. Although lung metastases show a slow rate of growth, approximately 10% of patients die from distant metastases. The radioresistance of ACC limits the efficacy of conventional radiotherapy for lung metastases, and the optimal dose remains to be determined. Stereotactic body radiotherapy (SBRT) using CyberKnife can deliver a high dose to the lung tumor, while sparing the surrounding normal lung tissues, leading to favorable local control in non-squamous cell lung cancer and metastatic lung tumors. We report a case of lung metastases from ACC treated successfully with SBRT using CyberKnife. Case presentation A 76-year-old Japanese man with ACC who was treated with carbon ion radiotherapy for a primary oropharynx tumor presented with three metastatic lesions in the lung. The tumor masses were located in the right upper, right lower, and left lower lobes of the lungs. Surgical resection was not indicated because of the presence of multiple tumors. The patient underwent SBRT at 60 Gy in 10 sequential fractions for each tumor. The biologically effective dose based on an alpha/beta ratio of 2 Gy was 240 Gy per tumor. The percentage of the total lung volume irradiated with >20 Gy was 4.9%, 3.2%, and 2.6% for each tumor. The patient developed acute radiation pneumonitis during the initial therapy, which resolved at 6 months after the CyberKnife treatment. At 21 months after the first CyberKnife treatment, three tumors showed no signs of recurrence. No late toxicity was observed. Conclusions SBRT using CyberKnife is an effective and feasible approach to the management of multiple lung metastases of ACC.

Micronuclei (MN) trigger antitumor immune responses via the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway. Radiotherapy induces MN in peripheral blood lymphocytes. However, data for solid tumors are lacking. Here, we analyzed MN post-radiotherapy in solid tumor samples. Tumor biopsy specimens were obtained from seven prospectively recruited patients with cervical cancer, before treatment and after receiving radiotherapy at a dose of 10 Gy (in five fractions). The samples were stained with 4′,6-diamidino-2-phenylindole dihydrochloride, and 200 nuclei per sample were randomly identified and assessed for the presence of MN or apoptosis, based on nuclear morphology. The median number of MN-harboring nuclei was significantly greater in samples from patients treated with radiotherapy than in pre-treatment samples (151 (range, 16–327) versus 28 (range, 0–61); p = 0.015). No significant differences in the number of apoptotic nuclei were observed between pre-treatment and 10 Gy samples (5 (range, 0–30) versus 12 (range, 2–30); p = 0.30). This is the first report to demonstrate MN induction by radiotherapy in solid tumors. The results provide clinical evidence of the activation of antitumor immune responses by radiotherapy.

This is a pooled analysis to evaluate the toxicity and efficacy of carbon-ion radiotherapy (C-ion RT) for inoperable endometrial carcinoma. Eligible patients had previously untreated Stage I–III endometrial carcinoma without para-aortic lymph node metastasis. Total dose to the tumor was 62.4–74.4 Gy [relative biological effectiveness (RBE)] in 20 fractions, and the dose to the gastrointestinal tract was limited to

Background and purpose We aimed to evaluate the relationship between brainstem necrosis and dose–volume histograms in patients with head and neck tumors after carbon-ion radiotherapy. Material and methods We evaluated 85 patients with head and neck tumors who underwent carbon-ion radiotherapy and were followed-up for ≥12 months. Brainstem necrosis was evaluated using the Common Terminology Criteria for Adverse Events (version 4.0). Results The median follow-up was 24 months, and four patients developed grade 1 brainstem necrosis, with 2-year and 3-year cumulative rates of 2.8% and 6.5%, respectively. Receiver operating characteristic curve analysis revealed the following significant cut-off values: a maximum brainstem dose of 48 Gy (relative biological effectiveness [RBE]), D1 cm 3 of 27 Gy (RBE), V40 Gy (RBE) of 0.1 cm 3 , V30 Gy (RBE) of 0.7 cm 3 , and V20 Gy (RBE) of 1.4 cm 3 . Multivariate analysis revealed that V30 Gy (RBE) was most significantly associated with brainstem necrosis. The 2-year cumulative rates were 33% and 0% for V30 Gy (RBE) of ≥0.7 cm 3 and 3 , respectively ( p Conclusions The present study indicated that the dose constraints might help minimize brainstem necrosis after carbon-ion radiotherapy.

To evaluate the efficacy and safety of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end-point was the 3-year local control rate, and the secondary end-points included the 3-year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time for all patients was 39 months. Thirty-two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3-year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2-3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon-ion radiotherapy achieved excellent local control and overall survival rates for non-squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.

In the era of precision medicine, radiotherapy strategies should be determined based on genetic profiles that predict tumor radiosensitivity. Accordingly, pre-clinical research aimed at discovering clinically applicable genetic profiles is needed. However, how a given genetic profile affects cancer cell radiosensitivity is unclear. To address this issue, we performed a pilot in vitro study by utilizing EGFR mutational status as a model for genetic profile. Clonogenic assays of EGFR mutant (n = 6) and wild-type (n = 9) non-small cell lung carcinoma (NSCLC) cell lines were performed independently by two oncologists. Clonogenic survival parameters SF2, SF4, SF6, SF8, mean inactivation dose (MID), D10, D50, α, and β were obtained using the linear quadratic model. The differences in the clonogenic survival parameters between the EGFR mutant and wild-type cell lines were assessed using the Mann–Whitney U test. As a result, for both datasets, the p values for SF2, SF4, D50, α, and α/β were below 0.05, and those for SF2 were lowest. These data indicate that a genetic profile of NSCLC cell lines might be predictive for their radiation response; i.e., EGFR mutant cell lines might be more sensitive to low dose- and low fraction sized-irradiation.

Purpose Three-dimensional image-guided brachytherapy (3D-IGBT) has become the standard therapy for patients with cervical cancer. However, in this population, the impact of 3D-IGBT in elderly individuals remains unknown. This study assessed the efficacy of 3D-IGBT for elderly patients with cervical cancer. Methods and Materials We performed a retrospective chart review of 105 consecutive patients with cervical squamous cell carcinoma aged ≥70 years who received radiotherapy alone between January 2001 and September 2014. All patients were treated with external beam radiotherapy and high-dose-rate intracavitary brachytherapy. We assessed the treatment outcomes in all patients. We then compared outcomes between two groups: patients treated by changing the Point A dose at brachytherapy (Group A, n = 71) and those treated with 3D-IGBT at least twice (Group B, n = 34). Results The median followup period was 59 (range, 6–203) months; the median age was 77 years. The 5-year local control and cause-specific survival rates were 89% and 78%, respectively. The 5-year cumulative rates of late toxicities of the rectum and bladder of Grade ≥3 were 2.0% and 4.2%, respectively. No statistically significant differences were observed in the local control and cause-specific survival rates, or in the incidence of rectal toxicities between groups. The 3-year cumulative rates of urinary toxicity of Grade ≥1 were 20.4% and 6.9% in Group A and Group B, respectively (p = 0.035). Conclusion In elderly patients with cervical cancer, 3D-IGBT could be performed safely and effectively and contributed to decreasing urinary toxicity incidence rates.

Background: Hypopharyngeal cancer is relatively rare disease and continues to have a poor prognosis. This study analyzed the efficacy and safety of radiotherapy for stage I-IVB hypopharyngeal cancer. Patients and Methods: Between 2000 and 2015, 72 patients were treated with definitive radiotherapy and 29 patients with stage IVA were treated with postoperative radiotherapy. Results: With definitive radiotherapy, the 3-year locoregional control rates for stage I-II, III, IVA, and IVB disease were 89%, 74%, 51% and 0%, respectively. The 3-year overall survival rates for patients with stage I-II, III, IVA and IVB disease were 84%, 89%, 55% and 15%, respectively. In patients with stage IVA disease treated with postoperative radiotherapy, 3-year locoregional control and overall survival rates were 83% and 75%, respectively, which were significantly better than those treated with definitive radiotherapy. Conclusion: Definitive radiotherapy was effective for stage I-III disease. Surgery and postoperative radiotherapy improved the survival rate of patients with stage IVA hypopharyngeal cancer.

Background/Aim: To evaluate the long-term outcomes of carbon-ion radiotherapy (C-ion RT) for locally advanced cervical squamous cell carcinoma (LAC-SqCC) in 2 prospective phase I/II studies. Patients and Methods: In the first study, 14 patients were treated with 68.8-72.8 Gy (RBE)/24 fractions. In a subsequent study, 22 patients were treated with 64.0-72.0 Gy (RBE)/20 fractions while limiting the dose to the gastro-intestinal (GI)

Human papillomavirus (HPV) infection is well known as a major etiological risk factor associated with carcinogenesis in uterine cervical cancer. However, few reports have investigated the association between HPV genotype and outcome in patients with uterine cervical cancer following radiotherapy (RT). The aim of the present study was to investigate the association between the HPV genotype and clinical outcome following RT in Japanese patients with uterine cervical cancer. Between November 2001 and August 2006, 157 Japanese women with uterine cervical cancer were treated with RT or concurrent chemoradiotherapy with curative intent. Pretreatment, formalin-fixed, paraffin-embedded biopsies were obtained from 83 patients. HPV genotypes were determined using the polymerase chain reaction method. Patients were categorized, according to HPV L1 protein sequence homology, into the HPV α-9 (HPV 16, 31, 33, 52, and 58), HPV α-7 (HPV 18, 39, 45, 59, and 68) or 'other' (HPV 51 and 56) groups. Associations between HPV genotype and clinical outcome following RT were evaluated. A total of 54 (65.1%) tumors were HPV α-9-positive, 13 (15.7%) were HPV α-7-positive, 2 (2.4%) were categorized under 'other' and 14 (16.9%) were HPV-negative. There were no significant differences in age, FIGO stage, regional lymph node metastases rate at diagnosis, or concurrent chemotherapy administration between the HPV α-9 and α-7 groups. The median follow-up period was 52 months (range, 2-156 months). The 5-year disease-free survival rates were 54.5 and 30.8% in the HPV α-9 and α-7 groups, respectively (P=0.034), and the 5-year distant metastasis rates were 38.0 and 69.2%, respectively (P=0.015). There were no significant differences in the 5-year local control or overall survival (OS) rates between the two groups. HPV genotype affected the 5-year distant metastatic rate, however not the 5-year local control or OS rate in patients with uterine cervical cancer following RT.

We conducted a phase 1/2 study to evaluate the efficacy and safety of carbon ion radiotherapy (C‐ion RT) with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma. Thirty‐three patients were enrolled between April 2010 and March 2014. Treatment consisted of C‐ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2. In the phase 1 component, the total dose was escalated from 68.0 Gy (relative biological effectiveness [RBE]) to 74.4 Gy (RBE) to determine the maximum tolerated dose of C‐ion RT. In the phase 2 component, the efficacy and safety of C‐ion RT with concurrent chemotherapy were evaluated using the dose determined in the phase 1 component. The median follow‐up duration was 30 months. Two patients did not receive chemotherapy because of anemia or leukocytopenia immediately prior to commencing treatment; 31 patients were analyzed. None of the patients developed dose‐limiting toxicities. The recommended dose (RD) was determined to be 74.4 Gy (RBE). In the phase 2 component, two patients developed Grade 3–4 toxicities in the gastrointestinal tract, due to repeated laser coagulation or peritonitis caused by appendicitis. In the patients treated with the RD, the 2‐year local control, progression‐free survival, and overall survival rates were 71%, 56%, and 88%, respectively. C‐ion RT with concurrent weekly cisplatin was well tolerated in patients with locally advanced uterine cervical adenocarcinoma. Our findings support further investigations into the efficacy of this strategy.

Research on ionizing radiation (IR)-induced clonogenic cell death is important for understanding the effect of IR on malignant tumors and normal tissues. Here, we describe a quick and cost-effective one-step assay for simultaneously assessing the major modes of clonogenic cell death induced by IR, i.e., apoptosis, mitotic catastrophe, and cellular senescence. In this method, cells grown on a cover slip are irradiated with X-rays and stained with 4',6-diamidino-2-phenylindole dihydrochloride (DAPI). Using fluorescence microscopy, apoptosis, mitotic catastrophe, and cellular senescence are identified based on the characteristic morphologies of the DAPI-stained nuclei. Apoptosis is determined by the presence of apoptotic bodies (i.e., condensed and fragmented nuclei). Mitotic catastrophe is determined by the presence of nuclei that exhibit two or more distinct lobes and micronuclei. Cellular senescence is determined by the presence of senescence-associated heterochromatic foci (i.e., nuclear DNA containing 30-50 bright, dense foci). This approach allows the experimenter to easily screen for clonogenic cell death modes using various cell lines, treatment settings, and/or time points, with the goal of elucidating the mechanisms of cell death in the target cells and conditions of interest.

In cancer therapy today, carbon ion radiotherapy is used mainly as monotherapy, whereas cisplatin is used concomitantly with X-ray radiotherapy. The effectiveness of concomitant carbon ions and cisplatin is unclear. To obtain the information on the mechanisms potentially shared between carbon ions or X-rays and cisplatin, we assessed the correlation of sensitivity to the single treatments. In 20 human cancer cell lines, sensitivity to X-rays strongly correlated with sensitivity to cisplatin, indicating the presence of potentially shared target mechanisms. Interestingly, the correlation of sensitivity to carbon ions and cisplatin was much weaker than that of sensitivity to X-rays and cisplatin, indicating the presence of potentially different target mechanisms between carbon ions and cisplatin. Assessment of clonogenic cell death by 4′,6-diamidino-2-phenylindole dihydrochloride staining showed that mitotic catastrophe was more efficiently induced by carbon ions than by the same physical dose of X-rays, while apoptosis and senescence were not. These data indicate that the correlation of sensitivity to carbon ions and cisplatin is weaker than that of sensitivity to X-rays and cisplatin, which are helpful as biological basis to understand the potentially shared mechanism among these treatments. Further investigation is mandatory to elucidate the clinical efficacy of carbon ions and cisplatin combination.

In the era of precision medicine, radiotherapy strategies should be determined based on genetic profiles that predict tumor radiosensitivity. Accordingly, pre-clinical research aimed at discovering clinically applicable genetic profiles is needed. However, how a given genetic profile affects cancer cell radiosensitivity is unclear. To address this issue, we performed a pilot in vitro study by utilizing EGFR mutational status as a model for genetic profile. Clonogenic assays of EGFR mutant (n = 6) and wild-type (n = 9) non-small cell lung carcinoma (NSCLC) cell lines were performed independently by two oncologists. Clonogenic survival parameters SF2, SF4, SF6, SF8, mean inactivation dose (MID), D10, D50, α, and β were obtained using the linear quadratic model. The differences in the clonogenic survival parameters between the EGFR mutant and wild-type cell lines were assessed using the Mann−Whitney U test. As a result, for both datasets, the p values for SF2, SF4, D50, α, and α/β were below 0.05, and those for SF2 were lowest. These data indicate that a genetic profile of NSCLC cell lines might be predictive for their radiation response; i.e., EGFR mutant cell lines might be more sensitive to low dose- and low fraction sized-irradiation.

Carbon ion radiotherapy shows great potential as a cure for X-ray-resistant tumors. Basic research suggests that the strong cell-killing effect induced by carbon ions is based on their ability to cause complex DNA double-strand breaks (DSBs). However, evidence supporting the formation of complex DSBs in actual patients is lacking. Here, we used advanced high-resolution microscopy with deconvolution to show that complex DSBs are formed in a human tumor clinically treated with carbon ion radiotherapy, but not in a tumor treated with X-ray radiotherapy. Furthermore, analysis using a physics model suggested that the complexity of radiotherapy-induced DSBs is related to linear energy transfer, which is much higher for carbon ion beams than for X-rays. Visualization of complex DSBs in clinical specimens will help us to understand the anti-tumor effects of carbon ion radiotherapy.

Background The purpose of this study was to compare carbon ion radiotherapy (C-ion RT) and stereotactic radiotherapy (SBRT) with photon beams for the treatment of hepatocellular carcinoma (HCC), specifically with regard to the dose volume parameters for target coverage and normal tissue sparing. Methods Data of 10 patients who were treated using C-ion RT with a total dose of 60 Gy(RBE) in four fractions were used. The virtual plan of SBRT was simulated on the treatment planning computed tomography images of C-ion RT. Dose volume parameters such as minimum dose covering 90 % of the planning target volume (PTV D90), homogeneity index (HI), conformity index (CI), mean liver dose (MLD), volume of the liver receiving 5 to 60 Gy (V5-60), and max point dose (Dmax) of gastrointestinal (GI) tract were calculated from both treatment plans. Results The PTV D90 was 59.6 ± 0.2 Gy(RBE) in C-ion RT, as compared to 56.6 ± 0.3 Gy in SBRT (p