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Supplementary Figure Legends 1-2 from Effects of Carbon Ion Beam on Putative Colon Cancer Stem Cells and Its Comparison with X-rays

Supplementary Figure 1 from Effects of Carbon Ion Beam on Putative Colon Cancer Stem Cells and Its Comparison with X-rays

The standard of treatment for esophageal cancer with adjacent organ invasion (T4) has not been established. We retrospectively analyzed the clinical outcomes of radiotherapy (RT) in elderly and younger patients with T4 esophageal cancer.Sixty-nine patients with T4 esophageal cancer who underwent RT at the Kanagawa Cancer Center between January 2014 and November 2020 were included in this study. Patients aged ≥70 years were defined as the elderly group and those aged70 years were defined as the younger group. The total dose of RT was set at 60 Gy in 30 fractions. Chemotherapy combined with 5-fluorouracil and cisplatin was administered concurrently with RT in general. The overall survival (OS) rate was estimated using the Kaplan-Meier method. Adverse events were assessed using CTCAE v4.0.The median survival time (MST) of the elderly group (n=35) was 21.5 months, and the OS rates at 1, 3, and 5 years were 63.7%, 31.3%, and 15.6%, respectively. The MST of the younger group (n=34) was 12.5 months, and the OS rates at 1, 3, and 5 years were 52.2%, 29.4%, and 29.4%, respectively. No significant difference in OS was observed between the two groups (p=0.767). Toxicities were not significantly different between the two groups except for thrombocytopenia and esophageal fistula (p=0.012 and p=0.022, respectively).The clinical outcomes of RT for T4 esophageal cancer in elderly patients were generally similar to those in the younger group.

Background/Aim: To evaluate treatment outcomes of carbon-ion radiotherapy for oropharyngeal non-squamous cell carcinoma at four carbon-ion facilities in Japan. Patients and Methods: We retrospectively analyzed the cases of 33 patients with oropharyngeal non-squamous cell carcinoma who were treated with carbon-ion radiotherapy between November 2003 and December 2014. Results: The histology included adenoid cystic carcinoma (n=25) and mucosal malignant melanoma (n=4). No patients had T1 tumors; 23 had T4 tumors. The most-commonly prescribed dose was 57.6 Gy (RBE) in 16 fractions. The median follow-up period was 34.8 months (range=4.2-122.8 months). The 3-year local control and overall survival rates were 94.7% and 90.7%, respectively. There were no grade ≥4 acute adverse events. Only one patient experienced a grade ≥4 late adverse event. No patients experienced late adverse events related to swallowing or salivary function. Conclusion: Carbon-ion radiotherapy appears to be a promising treatment option for oropharyngeal non-squamous cell carcinoma.

Purpose We analyzed interfractional robustness of scanning carbon ion radiotherapy (CIRT) for prostate cancer based on the dose distribution using daily in‐room computed tomography (CT) images. Materials and Methods We analyzed 11 consecutive patients treated with scanning CIRT for localized prostate cancer in our hospital between December 2015 and January 2016. In‐room CT images were taken under treatment conditions in every treatment session. The dose distribution on each in‐room CT image was recalculated, while retaining the pencil beam arrangement of the initial treatment plan. Then, the dose–volume histogram (DVH) parameters including the percentage of the clinical target volume (CTV) with 95% and 90% of the prescribed dose area (V95% of CTV, V90% of CTV) and V80% of rectum were calculated. The acceptance criteria for the CTV and rectum were set at V95% of CTV ≥95%, V90% of CTV ≥98%, and V80% of rectum < 10 ml. Results V95% of CTV, V90% of CTV, and V80% of rectum for the reproduced plans were 98.8 ± 3.49%, 99.5 ± 2.15%, and 4.39 ± 3.96 ml, respectively. Acceptance of V95% of CTV, V90% of CTV, and V80% of rectum was obtained in 123 (94%), 125 (95%) and 117 sessions (89%), respectively. Acceptance of the mean dose of V95% of CTV, V90% of CTV, and V80% of rectum for each patient was obtained in 10 (91%), 10 (91%), and 11 patients (100%), respectively. Conclusions We demonstrated acceptable interfractional robustness based on the dose distribution in scanning CIRT for prostate cancer.

Background/aim This study focused on the hybrid-volumetric modulated arc therapy (hVMAT) for stage I esophageal cancer and compared the effects on dose distribution induced by changes in the ratio of three-dimensional conformal radiotherapy (3DCRT) to VMAT. Patients and methods Fifteen patients who underwent 3DCRT for cT1bN0M0 esophageal cancer at Kanagawa Cancer Center from January 2014 to April 2019 were included in the study. The dose-volume histogram (DVH) parameters of the target volume and normal organs were evaluated in the 3DCRT, hVMAT, and VMAT treatment plans. Results The homogeneity index of the target volume was significantly lower for hVMAT. In hVMAT, as the ratio of VMAT increased, the volume of low-dose region in the heart and lung increased, whereas the volume of the middle- to high-dose region decreased. As the ratio of VMAT increased, the mean dose in the heart decreased, whereas the mean dose in the lung increased. Conclusion Favorable dose concentration was obtained for the target volume in hVMAT for stage I esophageal cancer. Altering the ratio of VMAT significantly changed the DVH parameters in normal organs.

Background This study evaluated carbon-ion radiotherapy (C-ion RT) for oral non-squamous cell carcinomas (non-SCC). Methods We retrospectively obtained data from 74 patients who underwent C-ion RT for oral malignancies between April 1997 and March 2016. The C-ion RT was administered in 16 fractions at a total dose of 57.6 or 64.0 Gy (relative biological effectiveness). Results Forty-three patients had salivary gland carcinomas, 29 patients had mucosal melanoma, and 2 patients had other types of pathologies. The tumors were classified as T1-T3 (24 cases), T4a (21 cases), or T4b (29 cases). The median follow-up was 49 months. The 5-year rates were 78.8% for local control, 36.2% for progression-free survival, and 58.3% for overall survival. Although 10 patients developed grade 3 osteoradionecrosis after C-ion RT, all patients maintained their mastication and deglutition functions after sequestrectomy and prosthesis placement. Conclusion C-ion RT was effective for oral non-SCC and had acceptable toxicities.

Background: This study evaluated carbon-ion radiotherapy (C-ion RT) for oral non-squamous cell carcmomas. Methods: We retrospectively obtained data from 74 patients who underwent C-ion RT for oral malignancies between April 1997 and March 2016. The C-ion RT was administered in 16 fractions at a total dose of 57.6 Gy or 64.0 Gy (relative biological effectiveness). Results: Forty-three patients had salivary gland carcinomas, 29 patients had mucosal melanoma, and 2 patients had other types of pathologies. The tumors were classified as Tl-T3 (24 cases), T4a (21 cases), or T4b (29 cases). The median follow-up was 49 months. The 5-year rates were 78.8% for local control, 36.2% for progression-free survival, and 58.3% for overall survival. Although 10 patients developed grade 3 osteoradionecrosis after C-ion RT, all patients maintained their mastication and deglutition functions after sequestrectomy and prosthesis placement. Conclusion: C-ion RT was effective for oral non-squamous cell carcinomas and had acceptable toxicities.

Background and purpose Usefulness of carbon ion radiotherapy (CIRT) for sacral chordoma has been reported from single institutions. We conducted a retrospective nationwide multicentre study to evaluate the clinical outcomes of CIRT for sacral chordoma in Japan. Materials and methods A total of 219 patients who underwent CIRT for sacral chordoma at institutions across Japan between December 2003 and July 2014 were included in this study. Results Median patient age was 67 years (range, 26–87 years). Most patients had no history of surgical resection (96%). The most frequent planning target volume (PTV) range was 100–500 mL (65%). The most frequently used dose-fractionation was 67.2 Gy (relative biological effectiveness) in 16 fractions (65%). The median follow-up was 56 months (range, 7–132 months). The 5-year overall survival (OS), progression-free survival, and local control rates were 84%, 48%, and 72%, respectively. Frequent sites of out-of-field recurrence included bone (9%) and lung (9%) metastases. The Cox proportional hazards model revealed that both younger age (P = 0.004) and smaller PTV (P = 0.001) were associated with significantly better OS. Acute toxicities of ≥Grade 3 occurred in eight patients (4%). Late toxicities of ≥Grade 3 occurred in 13 patients (6%): skin disorders in six patients (3%), pain in three (1%), myositis in three (1%), etc. Conclusion Our retrospective nationwide multicentre study showed that CIRT for sacral chordoma was effective and safe, and replicated the previously reported data from a representative CIRT institution in Japan demonstrating high local control and low toxicity rates.

Background/aim The present study aimed to compare the radiation dose distribution of carbon-ion radiotherapy (CIRT) for stage I esophageal cancer with three-dimensional conformal radiotherapy (3DCRT) and volumetric modulated arc therapy (VMAT). Patients and methods Fifteen patients with cT1bN0M0 esophageal cancer who received 3DCRT at Kanagawa Cancer Center between January 2014 and April 2019 were enrolled. The dose-volume histogram parameters of the target volume and normal organs planned with CIRT, 3DCRT, and VMAT were evaluated. Results The homogeneity index for the target volume of CIRT was significantly lower than that of 3DCRT and VMAT. In addition, the radiation dose of CIRT to the heart, lungs, spinal cord, and skin was significantly lower than that of 3DCRT and VMAT. Conclusion Favorable dose distributions with CIRT were demonstrated compared with 3DCRT and VMAT for esophageal cancer.

Carbon-ion radiotherapy (CIRT) has been reported to obtain favorable results in the treatment of bone and soft tissue malignancies; however, studies on CIRT for soft tissue sarcomas (STS) of the extremities are limited. Here, we have retrospectively evaluated the therapeutic efficacy and adverse events associated with scanning CIRT (sCIRT) for STS of the extremities at our institution.Thirteen consecutive patients with STS who underwent sCIRT between January 2017 and January 2020 were included in the study. The total dose of sCIRT was set at 67.2-70.4 Gy (RBE), which was provided in 16 fractions. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. Toxicity was evaluated using Common Terminology Criteria for Adverse Events v5.0.The cohort consisted of 10 males and 3 females with a median age of 69 years (range=38-95 years). Median duration of observation was 31.8 months (range=7.4-56.4 months). Tumors were localized to the upper extremity in 2 cases and to the lower extremity in 11 cases. Median maximum tumor diameter was 11.7 cm (range=3.0-36.6 cm), while 3-year OS, PFS, and LC were 61.5%, 44.9%, and 79.1%, respectively. Acute toxicity of grade 3 or higher was not observed. Late toxicity included grade 3 peripheral nerve palsy and decreased range of motion in 1 and 1 patient each. Late toxicity of Grade 4 or higher was not observed.sCIRT for STS of the extremities demonstrates favorable therapeutic results with acceptable toxicity.

Background To the authors' knowledge, carbon ion radiotherapy (CIRT) is one of the few curative treatments for unresectable pelvic bone sarcoma. The current study investigated the complications, functional outcomes, and risk factors of CIRT. Methods Of 112 patients who were treated with CIRT for unresectable pelvic bone sarcoma, the authors enrolled 29 patients who were without local disease recurrence or distant metastasis. The mean follow‐up was 93 months. Complications, functional outcomes, and quality of life scores were assessed. Risk factors were analyzed, including the dose‐volume histogram of the femoral head. Results Femoral head necrosis occurred in approximately 37% of patients, pelvic fractures were reported in 48% of patients, and neurological deficits were noted in 52% of patients. Femoral head necrosis was found to be significantly more prevalent among patients with periacetabular tumors (P = .018). The dose‐volume histogram of the femoral head indicated tolerable volume percentages of the femoral head to be 50 years and those with periacetabular tumors were found to have significantly lower Toronto Extremity Salvage Scores. Conclusions Femoral head necrosis, pelvic fracture, and nerve damage are common complications with the use of CIRT for pelvic bone sarcoma. To prevent femoral head necrosis, the radiation dose to the femoral head should be kept below the estimated tolerance curve presented in the current study. The functional outcome is nearly equivalent to that of surgery. CIRT may be a promising alternative to surgery for patients with unresectable pelvic bone sarcoma.

Background and purpose: Usefulness of carbon ion radiotherapy (CIRT) for sacral chordoma has been reported from single institutions. We conducted a retrospective nationwide multicentre study to evaluate the clinical outcomes of CIRT for sacral chordoma in Japan. Materials and methods: A total of 219 patients who underwent CIRT for sacral chordoma at institutions across Japan between December 2003 and July 2014 were included in this study. Results: Median patient age was 67 years (range, 26-87 years). Most patients had no history of surgical resection (96%). The most frequent planning target volume (PTV) range was 100-500 mL (65%). The most frequently used dose-fractionation was 67.2 Gy (relative biological effectiveness) in 16 fractions (65%). The median follow-up was 56 months (range, 7-132 months). The 5-year overall survival (OS), progression-free survival, and local control rates were 84%, 48%, and 72%, respectively. Frequent sites of out-of-field recurrence included bone (9%) and lung (9%) metastases. The Cox proportional hazards model revealed that both younger age (P = 0.004) and smaller PTV (P = 0.001) were associated with significantly better OS. Acute toxicities of ≥Grade 3 occurred in eight patients (4%). Late toxicities of ≥Grade 3 occurred in 13 patients (6%): skin disorders in six patients (3%), pain in three (1%), myositis in three (1%), etc. CONCLUSION: Our retrospective nationwide multicentre study showed that CIRT for sacral chordoma was effective and safe, and replicated the previously reported data from a representative CIRT institution in Japan demonstrating high local control and low toxicity rates.

To the authors' knowledge, carbon ion radiotherapy (CIRT) is one of the few curative treatments for unresectable pelvic bone sarcoma. The current study investigated the complications, functional outcomes, and risk factors of CIRT.Of 112 patients who were treated with CIRT for unresectable pelvic bone sarcoma, the authors enrolled 29 patients who were without local disease recurrence or distant metastasis. The mean follow-up was 93 months. Complications, functional outcomes, and quality of life scores were assessed. Risk factors were analyzed, including the dose-volume histogram of the femoral head.Femoral head necrosis occurred in approximately 37% of patients, pelvic fractures were reported in 48% of patients, and neurological deficits were noted in 52% of patients. Femoral head necrosis was found to be significantly more prevalent among patients with periacetabular tumors (P = .018). The dose-volume histogram of the femoral head indicated tolerable volume percentages of the femoral head to be33% for 40 grays (relative biological effectiveness) and 16% for 60 grays ( relative biological effectiveness). The mean Musculoskeletal Tumor Society score and Toronto Extremity Salvage Score were 53% and 64%, respectively, and the mean EuroQol 5 dimensions questionnaire index was 0.587. Patients aged50 years and those with periacetabular tumors were found to have significantly lower Toronto Extremity Salvage Scores.Femoral head necrosis, pelvic fracture, and nerve damage are common complications with the use of CIRT for pelvic bone sarcoma. To prevent femoral head necrosis, the radiation dose to the femoral head should be kept below the estimated tolerance curve presented in the current study. The functional outcome is nearly equivalent to that of surgery. CIRT may be a promising alternative to surgery for patients with unresectable pelvic bone sarcoma.

Background/Aim The efficacy and safety of carbon-ion radiotherapy (CIRT) for prostate cancer have already been demonstrated. The number of hemodialysis (HD) patients is increasing. Although the toxicity of CIRT in HD patients may be more severe, it has been insufficiently investigated. Therefore, we retrospectively analyzed the safety of CIRT for HD patients with prostate cancer in the present study. Materials and Methods Five HD patients with prostate cancer who underwent CIRT at the Kanagawa Cancer Center during November 2015–2020 were included in this study. CIRT was delivered by the raster scanning method (sCIRT). Adverse events were assessed using the CTCAE v5.0. The dose-volume histogram (DVH) parameters of the target volume and normal organs were evaluated between initial planning computed tomography (CT) and in-room CT images. Results In the acute phase, Grade 1 genitourinary toxicity was recorded in 1 patient. In the late phase, Grade 1 genitourinary toxicity was recorded in 2 patients. No gastrointestinal toxicities were noted during the follow-up period. In-room CT analysis revealed no significant differences among all DVH parameters of the target volume and normal organs when compared with the treatment plan dose. Conclusions The safety of sCIRT for prostate cancer in HD patients was investigated in the present study. In-room CT analysis suggested the robustness of the treatment plan. According to the present results, sCIRT for prostate cancer can be safely performed in HD patients.

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.

Background The reliability of DeepL Translator (DeepL GmbH, Cologne, Germany) for the translation for medical articles has not been verified yet. In this study, we investigated the accuracy of machine translation from Japanese to English for a medical article using the DeepL Translator. Methodology The subject of this study was an English-language medical article translated from Japanese, which had already been published. The original Japanese manuscript was translated into English using DeepL Translator. The translated English article was then back-translated into Japanese by three researchers. In turn, three other researchers compared the back-translated Japanese sentences with the original Japanese manuscript and calculated the percentage of sentences that retained the intended meaning. Results The mean ± standard deviation of the match rate for the entire article was 94.0 ± 2.9%. The match rate in the Results section was significantly higher than that in the other sections; while the match rate in the Materials and Methods section was significantly lower than the rate in the other sections. Compound sentences and sentences with an unclear subject and predicate appeared to be significant predictors for mismatched translation. Conclusions The translation for a medical article from Japanese to English was performed accurately by DeepL Translator.

Background/AimThe standard of treatment for esophageal cancer with adjacent organ invasion (T4) has not been established. Radiotherapy (RT) is a treatment option, but its efficacy and safety in elderly patients remains unclear. We retrospectively analyzed the clinical outcomes of RT in elderly and younger patients with T4 esophageal cancer.Materials and MethodsSixty-nine patients with T4 esophageal cancer who underwent RT at the Kanagawa Cancer Center between January 2014 and November 2020 were included in this study. Patients aged ≥70 years were defined as the elderly group and those aged ResultsThe median survival time (MST) of the elderly group was 21.5 months, and the OS rates at 1, 3, and 5 years were 63.7%, 31.3%, and 15.6%, respectively. The MST of the younger group was 12.5 months, and the OS rates at 1, 3, and 5 years were 52.2%, 29.4%, and 29.4%, respectively. A significant difference in OS was not observed between the two groups (p = 0.767). Themultivariate analysis revealed thatthe complete response (CR) of the primary tumor and adjuvant chemotherapy (ACTx) were significant predictors of OS (p< 0.001 andp = 0.012 and 0.022, respectively). Other toxicities were not significantly different between the two groups.ConclusionsOS was not significantly different between the elderly and younger groups. ACTx and CR were predictors of OS. The frequency of thrombocytopenia was higher in the elderly group and that of esophageal fistula was higher in the younger group. However, other toxicities were not significantly differentbetween the two groups.

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.

Time courses of the redox status in the brains of mice after X-ray or carbon-ion beam irradiation were observed by magnetic resonance redox imaging (MRRI). The relationship between radiation-induced oxidative stress on the cerebral nervous system and the redox status in the brain was discussed. The mice were irradiated by 8-Gy X-ray or carbon-ion beam (C-beam) on their head under anesthesia. C-beam irradiation was performed at HIMAC (Heavy-Ion Medical Accelerator in Chiba, NIRS/QST, Chiba, Japan). MRRI measurements using a blood-brain-barrier-permeable nitroxyl contrast agent, MCP or TEMPOL, were performed using 7-T scanner at several different times, i.e., 5–10 h, 1, 2, 4, and 8 day(s) after irradiation. Decay rates of the nitroxyl-enhanced T1-weighted MR signals in the brains were estimated from MRRI data sets, and variation in the decay rates after irradiation was assessed. The variation in decay rates of MCP and TEMPOL after X-ray or C-beam irradiation was similar, but different variation patterns were observed between X-ray and C-beam. The apparent decay rate of both MCP and TEMPOL decreased due to the temporal reduction of blood flow in the brain several hours after X-ray and/or C-beam irradiation. After decreasing, the apparent decay rates of nitroxyl radicals in the brain gradually increased during the following days after X-ray irradiation or rapidly increased 1 day after C-beam irradiation. The sequential increase in nitroxyl decay rates may have been due to the oxidative atmosphere in the tissue due to ROS generation. X-ray and C-beam irradiation resulted in different redox responses, which may have been due to time-varying oxidative stress/injury, in the mouse brain. The C-beam irradiation effects were more acute and larger than those of X-ray irradiation.

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.

Purpose This study evaluated the safety and efficacy of carbon-ion radiation therapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine cervical squamous cell carcinoma in a phase 1/2 clinical trial. Methods and Materials Twenty-two patients were treated with C-ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2. The phase 1 component evaluated the safety of 72.0 Gy (relative biological effectiveness) of C-ion RT with concurrent chemotherapy. In the phase 2 component, the safety and efficacy of C-ion RT with concurrent chemotherapy were assessed using the dose determined in phase 1. Results The median follow-up period was 32 months, and the median tumor size was 71 mm (range, 51-150 mm). No patient had dose-limiting toxicities in the phase 1 component; the recommended dose was determined to be 72.0 Gy (relative biological effectiveness) with 40 mg/m2 of cisplatin. In the phase 2 component, 2 patients developed grade 3 gastrointestinal tract toxicities. In patients treated with the recommended dose, the 2-year local control (LC), LC including salvage therapy, and overall survival rates were 67%, 81%, and 82%, respectively. The 2-year LC and overall survival rates for patients with tumor sizes ≤7.1 cm were 92% and 100%, respectively; for those with tumor sizes >7.1 cm they were 33% and 60%, respectively. Conclusions C-ion RT with concurrent weekly cisplatin was tolerated by patients with locally advanced uterine cervical squamous cell carcinoma. Outcomes were good in patients with tumor sizes ≤7.1 cm but not in those with larger tumors. The results of the present study should be validated with larger multi-institutional prospective studies. Further study is needed, and perhaps incorporating carbon ion external beam radiation with brachytherapy will further reduce the risk of central recurrence.

Purpose We investigated the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally recurrent rectal cancer (LRRC). Patients and methods Data from patients with LRRC treated with C-ion RT from November 2003 to December 2014 at three institutions were retrospectively analyzed. The endpoints of this clinical trial were overall survival (OS), local control (LC), and acute/late toxicity. Results A total of 224 patients' data were collected. The prescribed dose was 70.4 Gy (relative biological effectiveness [RBE]-weighted absorbed dose) or 73.6 Gy (RBE) in 16 fractions. The median follow-up period from the initiation of C-ion RT was 62 months (range 6–169 months). The OS rates were 73% (95% confidence interval [CI], 67%–79%) at 3 years and 51% (95%CI 44%–58%) at 5 years. The LC rates were 93% (95%CI 88%–96%) at 3 years, and 88% (95%CI 82%–93%) at 5 years. Grade 3 acute toxicity was observed in three patients: gastrointestinal toxicity (n = 1) and pelvic infection (n = 2). Grade 3 late toxicity was observed in 12 patients: skin reaction (n = 2), gastrointestinal toxicity (n = 2), neuropathy (n = 1), and pelvic infection (n = 7). There was no grade 4 or 5 acute or late toxicity. Conclusions This first multi-institutional analysis of C-ion RT for LRRC indicated relatively favorable outcomes with limited toxicities.

Even with its high RBE and >20 years history, there had been no breast cancer clinical trial using carbon-ion radiotherapy. We started a Phase I trial of carbon ion radiotherapy for Stage I breast cancer in 2013. This article describes the clinical and pathological evaluation of this study. Patients with low-risk Stage I breast cancer were eligible. A dose escalation study was designed, with dose levels of 48.0, 52.8 or 60.0 Gy relative biological effectiveness (RBE) administered in four fractions within 1 week. Three months after radiotherapy, the patients underwent tumor excision for pathological evaluation. Between April 2013 and December 2014, three cases receiving 48 Gy (RBE), three cases receiving 52.8 Gy (RBE) and one case receiving 60 Gy (RBE) underwent this protocol. No adverse effects were observed except for Grade 1 acute skin reaction in four cases. Pathological evaluation revealed that all four cases with doses of 52.8 Gy (RBE) and 60.0 Gy (RBE) achieved Grade 2b or more, but only two cases reached Grade 3. At the end of 2017, all cases were alive without recurrence or late had not caused any late adverse reaction. Carbon ion radiotherapy for Stage I breast cancer seems to be safe, and we found that it did not reach enough treatment effect 3 months after the treatment.

Background This study evaluated carbon‐ion radiotherapy (C‐ion RT) for oral non‐squamous cell carcinomas (non‐SCC). Methods We retrospectively obtained data from 74 patients who underwent C‐ion RT for oral malignancies between April 1997 and March 2016. The C‐ion RT was administered in 16 fractions at a total dose of 57.6 or 64.0 Gy (relative biological effectiveness). Results Forty‐three patients had salivary gland carcinomas, 29 patients had mucosal melanoma, and 2 patients had other types of pathologies. The tumors were classified as T1‐T3 (24 cases), T4a (21 cases), or T4b (29 cases). The median follow‐up was 49 months. The 5‐year rates were 78.8% for local control, 36.2% for progression‐free survival, and 58.3% for overall survival. Although 10 patients developed grade 3 osteoradionecrosis after C‐ion RT, all patients maintained their mastication and deglutition functions after sequestrectomy and prosthesis placement. Conclusion C‐ion RT was effective for oral non‐SCC and had acceptable toxicities.

The efficacy and safety of carbon‐ion radiotherapy (CIRT) for locally advanced non‐small‐cell lung cancer (LA‐NSCLC) remain unclear. We reported the clinical outcomes of CIRT for LA‐NSCLC. Data for 141 eligible patients who received CIRT between 1995 and 2015 were retrospectively analyzed. Local control (LC), locoregional control (LRC), progression‐free survival (PFS) and overall survival (OS) were calculated using the Kaplan‐Meier method. The median age was 75.0 years. Overall, 21 (14.9%), 57 (40.4%), 43 (30.5%) and 20 (14.2%) patients had T1, T2, T3 and T4 disease, respectively. Moreover, 51 (36.2%), 45 (31.9%), 40 (28.4%) and 5 (3.5%) patients had N0, N1, N2 and N3 disease, respectively. Furthermore, 34 (24.1%), 42 (29.8%), 45 (31.9%) and 20 (14.2%) patients had stages IIA, IIB, IIIA and ΙΙΙB disease, respectively. Overall, 62 (44.0%), 60 (42.6%), 8 (5.7%) and 11 (7.8%) patients had adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and others, respectively. The median dose was 72.0 Gy (relative biological effectiveness). No patient received concurrent chemotherapy. Median follow‐up periods were 29.3 (1.6‐207.7) and 40.0 (10.7‐207.7) months for all patients and survivors, respectively. Two‐year LC, PFS and OS rates were 80.3%, 40.2% and 58.7%, respectively. Overall, 1 (0.7%), 5 (3.5%) and 1 (0.7%) patient developed Grades 4 (mediastinal hemorrhage), 3 (radiation pneumonitis) and 3 (bronchial fistula) toxicities, respectively. Multivariate analysis showed adenocarcinoma and N2/3 classification as significant poor prognosticators of PFS. CIRT is an effective treatment with acceptable toxicity for LA‐NSCLC, especially for elderly patients or patients with severe comorbidities who cannot be treated with surgery or chemoradiotherapy.

Summary There is risk of mandibular osteoradionecrosis following external radiotherapy to tumors at the base of the tongue. To date, no report evaluates sparing of the mandibular bone offered by use of spacers. Here, we introduce and evaluate a custom-made mouthpiece employing a spacer for reduction of osteonecrosis following carbon-ion radiotherapy of tongue base tumors.

Background We conducted a retrospective multicenter study to assess the clinical outcomes of carbon‐ion radiotherapy (CIRT) for head and neck malignancies (Japan Carbon‐Ion Radiation Oncology Study Group [J‐CROS] study: 1402 HN). We aimed to evaluate the safety and efficacy of CIRT in patients with external auditory canal (EAC) and middle ear (ME) carcinomas. Methods Thirty‐one patients treated with CIRT at four Japanese institutions were analyzed. Fourteen patients (45.2%) had squamous cell carcinomas, 13 (41.9%) had adenoid cystic carcinomas, and four (12.9%) had other types. Nineteen (61.3%), six (19.4%), three (9.7%), and three (9.7%) patients had T4, T3, T2, and T1 disease, respectively. All patients had N0M0 status. The median radiation dose was 64 Gy (relative biological effectiveness) in 16 fractions. The median gross tumor volume was 33.3 mL. Results The median follow‐up period was 18.4 months (range, 5.1‐85.6). The 1‐ and 3‐year local control and overall survival rates were 75.0% and 55.0% and 79.3% and 58.7%, respectively. Regarding grade 3 or higher toxicities, three patients (9.7%) had grade 3 dermatitis, one (3.2%) had grade 3 mucositis, and two (6.5%) had grade 3 central nervous necrosis (ie, radiation‐induced brain necrosis). No grade 4 or worse reactions were observed. Conclusion CIRT was effective for EAC and ME carcinomas.

Background This study aimed to explain the dynamics of prostate-specific antigen (PSA) levels in patients with prostate cancer who were treated with carbon ion radiotherapy (CIRT) and neoadjuvant androgen-deprivation therapy (ADT). Methods Eighty-five patients with intermediate-risk prostate cancer who received CIRT and neoadjuvant ADT from December 2015 to December 2017 were analyzed in the present study. The total dose of CIRT was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. The PSA bounce was defined as a ≥0.4 ng/ml increase of PSA levels from the nadir, followed by any decrease. PSA failure was defined using the Phoenix criteria.Results The median patient age was 68 (range, 48–81) years. The median follow-up duration was 33 (range, 20–48) months. The clinical T stage was T1c, T2a, and T2b in 26, 44, and 14 patients, respectively. The Gleason score was 6 in 3 patients and 7 in 82 patients. The median pretreatment PSA level was 7.37 (range, 3.33–19.0) ng/ml. All patients received neoadjuvant ADT for a median of 6 (range, 2–116) months. PSA bounces were observed in 39 patients (45.9%), occurring a median of 12 (range, 6–30) months after CIRT. PSA failure was observed in eight patients (9.4%), occurring a median of 21 (range, 15–33) months after CIRT. The 3-year PSA failure-free survival rate was 88.5%. No clinical recurrence was observed during the follow-up period. Younger age was a significant predictor of PSA bounces and PSA failure. Conclusions The dynamics of PSA levels after CIRT was investigated in the present study. Further follow-up is needed to reveal the clinical significance of PSA dynamics.