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Radiation therapy (RT) for metastatic pelvic lymph nodes (PLNs) is not well established in cervical cancer. In this study the correlation between size of lymph nodes and control doses of RT was analyzed. Between January 2002 and December 2007, 245 patients with squamous cell carcinoma of the cervix treated with a combination of external beam irradiation with or without boost irradiation and high-dose rate brachytherapy were investigated. Size of lymph node was measured by computed tomography before RT and just after 50 Gy RT. Of the 245 patients, 78 had PLN metastases, and a total of 129 had enlarged PLNs diagnosed as metastases; 22 patients had PLN failure. The PLN control rate at 5 years was 79.5% for positive cases and 95.8% for negative cases. In cases with positive PLNs, 12 of 129 nodes (9.3%) developed recurrences. There was significant correlation between PLN control rate and size of PLN after 50 Gy ( 58 Gy had recurrence (P = 0.0003). These results suggested that the response of lymph nodes after RT was a more significant predictive factor for recurrence than size of lymph node before RT, and poor-response lymph nodes might require boost irradiation at a total dose of > 58 Gy.

Granulocyte-colony stimulating factor (G-CSF)-producing tumor is a rare condition. It has an aggressive nature and shows resistance to conventional treatments. We report two cases of G-CSF-producing uterine cervical cancer who were successfully treated with carbon-ion radiotherapy (C-ion RT). The first case was a 76-year-old woman with stage IIIB uterine cervical cancer, and the second was a 75-year-old woman with bulky stage IIB disease. Prior to treatment, both patients presented severe granulocytosis and elevated serum G-CSF concentrations. After C-ion RT, their cervical tumors completely disappeared, and their granulocytosis and elevated serum G-CSF levels improved as well. C-ion RT has been reported to be effective for various aggressive tumors, and it may be a good treatment option for this rare aggressive tumor.

Background and Purpose. Carbon-ion radiotherapy (C-ion RT) was effective therapy for inoperable spinal and paraspinal sarcomas. However, a significant adverse event following radiotherapies is vertebral compression fractures (VCFs). In this study, we investigated the incidence of and risk factors for post-C-ion RT VCFs in patients with spinal or paraspinal sarcomas. Material and Methods. Thirty consecutive patients with spinal or paraspinal sarcomas treated with C-ion RT were retrospectively reviewed. Various clinical parameters and the Spinal Instability Neoplastic Score (SINS) were used to evaluate the risk factors for post-C-ion RT VCFs. Results. The overall incidence of VCFs was 23% (median time: 7 months). Patients with VCFs showed a markedly higher SINS score (median value, 9 points) than those without VCF (5 points). The area under the receiver operating characteristic curve for the SINS score was 0.88, and the optimum SINS cut-off score was 8 points. The cumulative incidence of VCFs at 1 year was 9% for patients with a SINS score under 8 points, versus 80% for those with a SINS score of 8 points or higher (p<0.0001). Conclusions. In patients with a SINS score of 8 points or higher, referral to a spine surgeon for stabilization and multidisciplinary discussion is appropriate.

Purpose Head and neck (HN) adenocarcinoma is rare, and to date, there have been no reports of prospective studies. We retrospectively evaluated the efficacy and safety of carbon-ion radiation therapy (C-ion RT) for HN adenocarcinoma in institutions in Japan. Methods and Materials HN adenocarcinoma patients with N0M0 or N1M0 disease who were treated with C-ion RT at institutions in Japan between November 2003 and December 2014 were analyzed retrospectively. We enrolled 47 patients (30 male and 17 female patients; median age, 60 years) with HN adenocarcinoma. Results Primary sites included the nasal and paranasal sinus in 21 patients, orbit in 11, salivary grand in 7, oral cavity and pharynx in 6, and acoustic organ in 2. Thirty-two patients had T4 tumors, 6 had T3, and 6 had T2. Forty-five patients received a diagnosis of N0 disease, whereas 2 had N1 disease. The median total dose of C-ion RT and the number of fractions were 64.0 Gy (relative biological effectiveness) and 16 fractions, respectively. The median follow-up period was 51 months (range, 6-118 months). The 2- and 5-year overall survival rates were 87.9% and 60.4%, respectively, and the 2- and 5-year local control rates were 83.3% and 79.3%, respectively. Multivariate analysis showed that operability (patients with operable tumors) ( P =.045) and fractionation (16 fractions) ( P =.010) were significant independent prognostic factors for better overall survival. No grade 5 late morbidities were observed. Grade 4 late morbidities were observed in 4 patients, and all of these grade 4 morbidities were visual impairments. All 4 patients with grade 4 visual impairment had T4 tumors in the nasopharynx or paranasal sinuses, which implied inoperable tumors with orbital or brain invasion. Conclusions C-ion RT resulted in excellent local control. C-ion RT could become a curative treatment option for HN adenocarcinoma with acceptable toxicities.

Background The safety and effectiveness of carbon-ion radiotherapy (CIRT) for isolated para-aortic lymph node (PALN) metastasis was evaluated retrospectively. Methods CIRT for isolated PALN metastasis from CRC was performed in 34 cases from June 2006 to August 2015 in our institute. A median dose of 52.8 Gy(RBE) (range, 48-52.8 Gy(RBE)) was delivered with a median daily dose of 4.4 Gy(RBE) (range, 4.0-4.4 Gy(RBE)). Results The median follow-up duration for all patients was 24.4 months (range, 7-82.8 months). There were 13 cases (38.2%) who achieved complete response after treatment. The local control rates at 2 and 3 years were 70.1% and 70.1%, respectively. The overall survival rates at 2 and 3 years were 83.3% and 63.0%, respectively. The 3-year survival rates for Stage I-III were 68.7%, while those for Stage IV was 0%. The overall survival of cases with rectal cancer or with high CA19-9 values pre-CIRT tended to be worse. The median survival period was 41.7 months. Twelve of the 34 patients survived for more than 3 years. There were no adverse effects of Grade 3 or higher. Conclusions CIRT for isolated PALN recurrence after curative resection for CRC appears effective and safe, and it is considered a promising therapy.

The aim of this study was to prospectively assess 5-year health-related quality of life (HRQOL) of patients treated with carbon ion radiotherapy (C-ion RT) for clinically localized prostate cancer. A total of 417 patients received carbon ion radiotherapy at a total dose of 63–66 Gray-equivalents (GyE) in 20 fractions over 5 weeks, and neoadjuvant and adjuvant androgen deprivation therapy (ADT) were administered for intermediate and high-risk patients. A HRQOL assessment was performed at five time points (immediately before the initiation of C-ion RT, immediately after, and at 12, 36 and 60 months after completion of C-ion RT) using Functional Assessment of Cancer Therapy (FACT) questionnaires. FACT-G and FACT-P scores were significantly decreased; however, the absolute change after 60 months was minimal. The transient decreases in the Trial Outcome Index (TOI) score returned to their baseline levels. Use of ADT, presence of adverse events, and biochemical failure were related to lower scores. Scores of subdomains of FACT instruments indicated characteristic changes. The pattern of HRQOL change after C-ion RT was similar to that of other modalities. Further controlled studies focusing on a HRQOL in patients with prostate cancer are warranted.

Purpose To evaluate the efficacy and safety of carbon-ion radiation therapy (RT) for mucosal melanoma of the head and neck (MMHN) in the Japan Carbon-Ion Radiation Oncology Study Group study. Methods and Materials Patients with MMHN with N0-1M0 status who were treated with carbon-ion RT at 4 institutions in Japan between November 2003 and December 2014 were analyzed retrospectively. Two hundred sixty patients (male, 111; female, 149; median age, 68 years) with histologically proven MMHN were enrolled. Results Primary sites included the nasal cavity in 178 patients, paranasal sinuses in 43, oral cavity in 27, and pharynx in 12. Eighty-six patients had T3 tumors, 147 had T4a tumors, and 27 had T4b tumors. Two hundred fifty-one patients were diagnosed with N0 disease, and 9 with N1 disease. The median total dose and number of fractions were 57.6 Gy RBE (relative biological effectiveness) and 16, respectively. Chemotherapy including dimethyl traizeno imidazole carboxamide was used concurrently in 129 patients. The median follow-up duration was 22 months (range, 1-132 months). The 2-year overall survival and local control rates were 69.4% and 83.9%, respectively. Multivariate analysis showed that gross tumor volume and concurrent chemotherapy were significant prognostic factors for overall survival. Grade 3 and grade 4 late morbidities were observed in 27 and 7 patients (5 developed ipsilateral blindness, 1 mucosal ulcer, and 1 second malignant disease in the irradiated volume), respectively. No patients developed grade 5 late morbidities. Conclusion Carbon-ion RT is a promising treatment option for MMHN.

The purpose of this study was to present our evaluation of the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for locally advanced parotid gland carcinomas.Clinicopathological features and outcomes were evaluated in 46 patients receiving C-ion RT for parotid gland carcinomas.Sixteen patients had adenoid cystic carcinoma; 8 had adenocarcinoma, 8 had mucoepidermoid carcinoma, and 14 had other carcinomas. T2, T3, T4a, and T4b diseases were diagnosed in 3, 18, 8, and 17 patients, respectively. C-ion RT was provided to 25 patients as the primary treatment, to 20 patients for local recurrences after surgery, and to 1 patient for residual tumor after surgery. During follow-up (median duration, 62 months), 5-year local control and overall survival (OS) rates were 74.5% and 70.1%, respectively. Of the 30 patients without facial nerve palsy before C-ion RT, 25 showed no radiation-induced facial nerve palsy.C-ion RT is effective and has acceptable toxicity levels for locally advanced parotid gland carcinomas. © 2016 Wiley Periodicals, Inc. Head Neck 39: 724-729, 2017.

Purpose To determine the effectiveness of carbon ion radiotherapy (CIRT) for localized primary sarcomas of the extremities in a prospective study. Patients and materials From April 2000 to May 2010, 17 (male/female: 12/5) patients with localized primary sarcoma of the extremities received CIRT. The median age was 53years (range: 14–87years). Nine patients had primary diseases and eight had recurrent diseases. Of the 17 patients, eight refused amputation, and the remaining nine refused surgical resection. Tumors were located in the upper limbs in four patients and lower limbs in 13. Histological diagnosis was osteosarcoma in three patients, liposarcoma in two, synovial sarcoma in two, rhabdomyosarcoma in two, pleomorphic sarcoma in two, and miscellaneous in six. The CIRT dose to the limb was 52.8GyE for one patient, 64GyE for three, 70.4GyE for 13 in 16 fixed fractions over 4weeks. Records were reviewed and outcomes including radiologic response, local control (progression-free), and survival were analyzed. Results The median follow-up was 37months (range: 11–97months). Radiological response rate was 65% (PR in 11, SD in 5, and PD in 1). The local control rate at 5years was 76%. The overall survival rate at 5years was 56%. Of the 17 patients, 10 survived without disease progression. Four patients had local recurrences, one was salvaged by repeated CIRT and the other three died due to systemic diseases. Distant failure was observed in six patients. One patient suffered from femoral fracture (grade 3) and received surgical fixation 27months after CIRT. No other severe reactions (grade 3) were observed. Conclusions CIRT is suggested to be an effective and safe treatment for patients who refuse surgery for localized primary sarcomas of the extremities.

PURPOSE: To assess the effects of differences in dose fractionation on late radiation toxicity and biochemical control in patients with prostate cancer treated with carbon ion radiotherapy (C-ion RT). \nMETHODS AND MATERIALS: A total of 740 prostate cancer patients who received C-ion RT between April 2000 and February 2009 were analyzed. Of those, 664 patients followed for at least 1 year were analyzed with regard to late radiation toxicity. Biochemical relapse-free (BRF) and overall survival (OS) rates in patient subgroups with each dose-fractionation were analyzed. \nRESULTS: Only 1 case of grade 3 genitourinary (GU) morbidity was observed in 20 fractions, and none of the patients developed higher grade morbidities. The incidence of late GU toxicity in patients treated with 16 fractions was lower than that of patients treated with 20 fractions. The OS rate and BRF rate of the entire group at 5 years were 95.2% and 89.7%, respectively. The 5-year BRF rate of the patients treated with 16 fractions of C-ion RT (88.5%) was comparable to that of the patients treated with 20 fractions (90.2%). \nCONCLUSION: C-ion RT of 57.6 GyE (the physical C-ion dose [Gy] x RBE) in 16 fractions could offer an even lower incidence of genitourinary toxicity and comparable BRF rate than that in 20 fractions. Advancement in hypofractionation could be safely achieved with C-ion RT for prostate cancer.

In carbon ion radiotherapy there is an urgent clinical need to develop objective tools for the conversion of relative biological effectiveness (RBE)-weighted doses based on different models. In this work we introduce a clinically oriented method to compare NIRS-based and LEM-based GyE systems, minimizing differences in physical dose distributions between treatment plans. Carbon ion plans were optimized on target volumes of cubic and spherical shapes, for RBE-weighted dose prescription levels ranging from 3.6 to 4.4 GyE. Plans were calculated for target sizes from 4 to 12 cm defining three beam geometries: single beam, opposed beam and orthogonal beam configurations. The two treatment planning systems currently employed in clinical practice were used, providing the NIRS-based and LEM-based GyE calculations. Physical dose distributions of NIRS-based and LEM-based treatment plans were compared. LEM-based prescription doses that minimize differences in physical dose distributions between the two systems were found. These doses were compared with the mean RBE-weighted dose obtained with a Monte Carlo code (FLUKA) interfaced with LEM I. In the investigated dose range, LEM-based RBE-weighted prescription doses, that minimize differences with NIRS plans, should be higher than NIRS reported prescription doses. The optimal dose depends on target size, shape and position, number of beams and dose level. The opposed beam configuration resulted in the smallest average prescription dose difference (0.45 ± 0.09 GyE). The second approach of recalculating NIRS RBE-weighted dose with a Monte Carlo code interfaced with LEM resulted in no significant difference with the results obtained from the planning study. The delivery of a voxel by voxel iso-effective plan, if different RBE models are employed, is not feasible; it is however possible to minimize differences in a treatment plan with the simple approach presented here. Dose prescription ultimately represents a clinical task under the responsibility of the radiation oncologist, the presented analysis intends to be a quantitative and objective way to assist the clinical decision.

Our institute has constructed a new treatment facility for carbon ion scanning beam therapy. The first clinical trials were successfully completed at the end of November 2011. To evaluate patient setup accuracy, positional errors between the reference Computed Tomography (CT) scan and final patient setup images were calculated using 2D-3D registration software. Eleven patients with tumors of the head and neck, prostate and pelvis receiving carbon ion scanning beam treatment participated. The patient setup process takes orthogonal X-ray flat panel detector (FPD) images and the therapists adjust the patient table position in six degrees of freedom to register the reference position by manual or auto- (or both) registration functions. We calculated residual positional errors with the 2D-3D auto-registration function using the final patient setup orthogonal FPD images and treatment planning CT data. Residual error averaged over all patients in each fraction decreased from the initial to the last treatment fraction [1.09 mm/0.76° (averaged in the 1st and 2nd fractions) to 0.77 mm/0.61° (averaged in the 15th and 16th fractions)]. 2D-3D registration calculation time was 8.0 s on average throughout the treatment course. Residual errors in translation and rotation averaged over all patients as a function of date decreased with the passage of time (1.6 mm/1.2° in May 2011 to 0.4 mm/0.2° in December 2011). This retrospective residual positional error analysis shows that the accuracy of patient setup during the first clinical trials of carbon ion beam scanning therapy was good and improved with increasing therapist experience.

The purpose of this prospective study was to assess the prognostic value of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography/computed tomography (PET/CT) for the outcome of carbon ion radiotherapy (CIRT) in patients with mucosal malignant melanoma (MMM) of the head and neck.Thirteen patients (69 ± 13 years) with histologically proven MMM tumor were enrolled. CIRT was performed with a total dose of 57.6-64.0 gray equivalents per 16 fractions over a period of 4 weeks. FLT-PET/CT was performed before and again 1 month after CIRT. Tumor FLT uptake was quantitatively assessed using the maximum standardized uptake value (SUV(max)). FLT-PET parameters [pre-CIRT SUV(max), post-CIRT SUV(max), and the reduction rate (RR)] and clinical parameters [age, gender, tumor site, tumor status, gross tumor volume (GTV), and regional lymph node involvement] were evaluated in relation to survival estimates. The follow-up period was 16.1 ± 5.9 months for 9 deceased patients, and 36.7 ± 7.9 months for 4 survivors.Pre-CIRT SUV(max) of ≥4.3, age of ≥80 years old, sinonasal cavity tumor site, and GTV of ≥39 mL were found to be statistically significant prognostic factors for better overall survival. Pre-CIRT SUV(max) of ≥5.0, age of ≥80 years old, sinonasal cavity tumor site, and the absence of regional lymph node involvement were statistically significant prognostic factors for better metastasis-free survival. RR of ≥35 % and GTV of73 mL were predictive of better local control.The present study indicated for the first time that in patients with the head and neck MMM, FLT-PET/CT imaging was useful for predicting the therapeutic outcome of CIRT. Our results will contribute to the establishment of an effective staging system for MMM based on prognostic factors, depending on treatment choice.

BACKGROUND: The authors evaluated the tolerance and efficacy of carbon-ion radiotherapy (CIRT) as a short-course, preoperative treatment and determined the recommended dose needed to reduce the risk of postoperative local recurrence without excess injury to normal tissue. METHODS: Patients radiographically defined with potentially resectable pancreatic cancer were eligible. A preoperative, short-course, dose-escalation study was performed with fixed 8 fractions in 2 weeks. The dose of irradiation was increased by 5% increments from 30 grays equivalents (GyE) to 36.8 GyE. Surgery was to be performed 2 to 4 weeks after the completion of CIRT. RESULTS: The study enrolled 26 patients. At the time of restaging after CIRT, disease progression with distant metastasis or refusal ruled out 5 patients from surgery. Twenty-one of 26 patients (81%) patients underwent surgery. The pattern of initial disease progression was distant metastasis in 17 patients (65%) and regional recurrence in 2 patients (8%). No patients experienced local recurrence. The 5-year survival rates for all 26 patients and for those who underwent surgery were 42% and 52%, respectively. CONCLUSIONS: Preoperative, short-course CIRT followed by surgery is feasible and tolerable without unacceptable morbidity. Cancer 2013. © 2012 American Cancer Society.

Purpose To evaluate the efficacy of carbon ion radiotherapy for head-and-neck cancer in a phase II clinical trial. Materials and methods Between April 1997 and February 2006, 236 patients with locally advanced, histologically proven, and new or recurrent cancer of the head and neck were treated with carbon ions. The treatment dose was 64.0GyE/16 fractions/4weeks (or 57.6GyE/16 fractions/4weeks when the wide-range skin was included in the target volume). Results There were grade 3 acute skin reactions in 6% and grade 3 acute mucosal reactions in 10% with no acute reactions worse than grade 3, and grade 2 late skin reactions in 3% and grade 2 late mucosal reactions in 2% with no late reactions worse than grade 2. The 5-year local control rate, by histological type, was 75% for the 85 patients with malignant melanoma, 73% for the 69 with adenoid cystic carcinoma, 73% for the 27 with adenocarcinoma, 61% for the 13 with papillary adenocarcinoma, 61% for the 12 with squamous cell carcinoma and 24% for the 14 with sarcomas. The 5-year over-all survival rate was 68% for adenoid cystic carcinoma, 56% for adenocarcinoma and 35% for malignant melanoma. Conclusions Carbon ion radiotherapy for head and neck cancer showed the therapeutic effectiveness for malignant melanoma and adenoid cystic carcinoma without severe morbidity of the normal tissues.

BACKGROUND: The authors summarized the outcomes of patients with unresectable osteosarcoma of the trunk who received carbon ion radiotherapy (CIRT). METHODS: The authors performed a retrospective analysis of 78 patients who had medically inoperable osteosarcoma of the trunk and received treatment with CIRT between 1996 and 2009. Tumor sites included the pelvis in 61 patients, the spine and paraspinal region in 15 patients, and other sites in 2 patients. The median applied CIRT dose was 70.4 Gray equivalent (GyE) in a total of 16 fixed fractions over 4 weeks. RESULTS: The minimum duration of follow-up for survivors was 14 months. Forty-eight patients remained alive. The 5-year overall survival rate was 33%, and the local control rate was 62%. Thirty-eight patients who had a clinical target volume 5 years, 8 were able to walk with or without the help of a cane, and 6 were free from pain killers. CONCLUSIONS: CIRT appeared to be a safe and effective modality for the management of unresectable osteosarcoma of the trunk, providing good local control and offering a survival advantage and good long-term functional results without unacceptable morbidity. Cancer 2012. © 2012 American Cancer Society.

In 1994, carbon-ion radiotherapy was started at the National Institute of Radiological Sciences using the Heavy-Ion Medical Accelerator in Chiba. Between June 1995 and March 2000, two phase I/II dose escalation studies (protocols 9402 and 9703) of hypofractionated carbon-ion radiotherapy for both early- and advance-stage prostate cancer patients had been carried out to establish radiotherapy technique and to determine the optimal radiation dose. To validate the feasibility and efficacy of hypofractionated carbon-ion radiotherapy, a phase II study (9904) was initiated in April 2000 using the shrinking field technique and the recommended dose fractionation (66 gray equivalents in 20 fractions over 5 weeks) obtained from the phase I/II studies, and was successfully completed in October 2003. The data from 175 patients in the phase II study showed the importance of an appropriate use of androgen deprivation therapy according to tumor risk group. Since November 2003, carbon-ion radiotherapy for prostate cancer was approved as "Highly Advanced Medical Technology" from the Ministry of Health, Labor, and Welfare, and since then approximately 1100 patients have received carbon-ion radiotherapy as of July 2011. In this review, we introduce our steps thorough three clinical trials carried out at National Institute of Radiological Sciences, and show the updated data of carbon-ion radiotherapy obtained from approximately 1000 prostate cancer patients. In addition, our recent challenge and future direction will be also described.

Background Carbon-ion radiotherapy (CIR) has been under development. We report the results of a phase I/II clinical trial of preoperative CIR for esophageal squamous cell carcinoma (ESCC). Methods Thirty-one thoracic ESCC patients were enrolled. They were first treated with CIR. The radiation dose was escalated from the initial dose of 28.8 GyE up to 36.8. Four to 8 weeks after CIR followed by clinical evaluation of the therapy, surgery was performed. Thereafter, a pathological evaluation was made. Results Acute toxicity was not seen except in one case (3.2%), and there were no late toxicities. Throughout the study period, there were no cases of withdrawal due to the effects of preoperative CIR. Twelve out of 31 (38.7%) patients achieved a clinical complete response (CR) and 13 patients (41.9%) achieved a partial response. Twelve out of 31 patients (38.7%) achieved a pathological CR. The overall 1-, 3-, and 5-year survival rates in the stage I cases were 91%, 81%, and 61%, and was 100%, 85%, and 77% for the stage II, and 71%, 43%, and 29% for the stage III cases, respectively. Conclusions CIR showed strong local tumor control and is highly effective as a neoadjuvant therapy without severe adverse events. J. Surg. Oncol. 2012; 105:750–755. © 2011 Wiley Periodicals, Inc.

Purpose To evaluate the efficacy, post-treatment function, toxicity, and complications of carbon ion radiotherapy (RT) for sacral chordoma compared with surgery. Methods and Materials The records of 17 primary sacral chordoma patients treated since 1990 with surgery ( n =10) or carbon ion RT ( n =7) were retrospectively analyzed for disease-specific survival, local recurrence-free survival, complications, and functional outcome. The applied carbon ion dose ranged from 54.0 Gray equivalent (GyE) to 73.6 GyE (median 70.4). Results The mean age at treatment was 55 years for the surgery group and 65 years for the carbon ion RT group. The median duration of follow-up was 76 months for the surgery group and 49 months for the carbon ion RT group. The local recurrence-free survival rate at 5 years was 62.5% for the surgery and 100% for the carbon ion RT group, and the disease-specific survival rate at 5 years was 85.7% and 53.3%, respectively. Urinary-anorectal function worsened in 6 patients (60%) in the surgery group, but it was unchanged in all the patients who had undergone carbon ion RT. Postoperative wound complications requiring reoperation occurred in 3 patients (30%) after surgery and in 1 patient (14%) after carbon ion RT. The functional outcome evaluated using the Musculoskeletal Tumor Society scoring system revealed 55% in the surgery group and 75% in the carbon ion RT group. Of the six factors in this scoring system, the carbon ion RT group had significantly greater scores in emotional acceptance than did the surgery group. Conclusion Carbon ion RT results in a high local control rate and preservation of urinary-anorectal function compared with surgery.

Background and purpose To evaluate the potential of apparent diffusion coefficient (ADC) value before carbon ion radiotherapy (C-ion RT) for malignant mucosal melanoma (MMM) to predict prognosis. Materials and methods We recruited 37 patients with MMM in the head and neck treated by C-ion RT with concomitant chemotherapy. Univariate and multivariate analyses of minimum ADC, mean ADC, tumor volume, age, PS, and gender were performed to identify prognostic factors. Results The 3-year local control rate, distant metastasis-free survival rate and overall survival rate of all patients were 81.1%, 37.6% and 65.3%, respectively, with a median follow-up period of 19.0months. In univariate analyses, lower minimum ADC (⩽0.6380×10 −3 mm 2 /s) and lower mean ADC (⩽1.1523×10 −3 mm 2 /s) were unfavorable prognostic factors for distant metastasis ( p =0.029 and p =0.014, respectively), and lower minimum ADC was an unfavorable prognostic factor for overall survival ( p =0.019). However, there was no significant prognostic factor of local control including ADC value. In multivariate analyses, only minimum ADC was selected as a prognostic factor of distant metastasis-free survival and overall survival ( p =0.015 and p =0.006, respectively). Conclusion Minimum ADC can be a prognostic factor of MMM in the head and neck after C-ion RT.

Background and purpose To compare the efficacy and toxicity of short-course carbon ion radiotherapy (C-ion RT) for patients with hepatocellular carcinoma (HCC) in terms of tumor location: adjacent to the porta hepatis or not. Materials and methods The study consisted of 64 patients undergoing C-ion RT of 52.8GyE in four fractions between April 2000 and March 2003. Of these patients, 18 had HCC located within 2cm of the main portal vein (porta hepatis group) and 46 patients had HCC far from the porta hepatis (non-porta hepatis group). We compared local control, survival, and adverse events between the two groups. Results The 5-year overall survival and local control rates were 22.2% and 87.8% in the porta hepatis group and 34.8% and 95.7% in the non-porta hepatis group, respectively. There were no significant differences ( P= 0.252, P =0.306, respectively). Further, there were no significant differences in toxicities. Biliary stricture associated with C-ion RT did not occur. Conclusions Excellent local control was obtained independent of tumor location. The short-course C-ion RT of 52.8GyE in four fractions appears to be an effective and safe treatment modality in the porta hepatis group just as in the non-porta hepatis group.

Background and purpose To examine whether liver volume changes affect prognosis and hepatic function in patients treated with carbon ion radiotherapy (CIRT) for hepatocellular carcinoma (HCC). Material and methods Between April 1995 and March 2003, among the cases treated with CIRT, 43 patients with HCC limited to the right hepatic lobe were considered eligible for the study. The left lateral segment was defined as the non-irradiated region. Liver volume was measured using contrast CT at 0, 3, 6, and 12months after CIRT. We examined serum albumin, prothrombin activity, and total bilirubin level as hepatic functional reserve. Results After CIRT, the non-irradiated region showed significant enlargement, and enlarged volume of this region 3months after CIRT ⩾50cm 3 was a prognostic factor. The 5-year overall survival rates were 48.9% in the larger enlargement group (enlarged volume of non-irradiated region 3months after CIRT ⩾50cm 3 ) and 29.4% in the smaller enlargement group (as above, 3 ). The larger enlargement group showed better hepatic functional reserve than the smaller enlargement group 12months after CIRT. Conclusions This study suggests that compensatory enlargement in the non-irradiated liver after CIRT contributes to the improvement of prognosis.

OBJECTIVE: Standardized uptake value (SUV) is affected by many factors. In that respect, the brain reference index (BRI: regions of interest of tumor/regions of interest of cerebellum) is one of the quantitative approaches to eliminate the variety of factors that affect SUV. MRI pulse sequence findings can also provide information about tissue cellularity. This information is useful for evaluating the malignancy of lesions. We evaluated the role of glucose metabolism and cellularity for the diagnosis of pancreatic tumor malignancy. METHOD: We performed a radionuclide 2-(18)F-fluoro-2-deoxyglucose ((18)F-FDG) uptake analysis and a signal intensity analysis using MRI on 16 presurgery patients with either proven or suspected pancreatic cancer. The tumor glucose metabolism was evaluated with SUV and BRI in an FDG-PET study. Tumor cellularity was determined with the MRI factors, apparent diffusion coefficient (ADC), T2 value and tumor to nontumor ratio of proton density. We compared these results with the pathological findings. RESULTS: SUV (= 0.855), BRI ( =0.875), and ADC ( =0.830) showed a larger the area under the curve than T2 value (= 0.582) and tumor to nontumor ratio of proton density ( = 0.786) according to the receiver operating characteristics analysis, and we therefore considered that these three factors were better indexes for the diagnosis of tumor malignancy. SUV and BRI had a high specificity. In contrast, ADC had a high sensitivity. CONCLUSION: The glucose metabolism with PET/CT and cellularity with MRI are different indexes for the diagnosis of tumor malignancy. Both provide necessary information for making an accurate diagnosis. Using both types of information may therefore help in obtaining a highly accurate diagnosis.

Seventy patients having squamous-cell carcinoma of the uterine cervix FIGO Stage I-II with negative lymph nodes and positive parametrial involvement received postoperative radiotherapy following radical hysterectomy and pelvic lymphadenectomy. In 48 patients with microscopic parametrial invasion, the 5-year survival rate was 92%. The other 22 patients with macroscopic parametrial involvement had a 5-year survival rate of 75%. The overall recurrence rate was 13% (9 of 70). The sites of failure were 3 pelvic alone, 5 distant metastases alone, and 1 combined pelvis and para-aortic lymph node. All of those with recurrence were Stage-II cases. The absolute pelvic-control rate was 94.3% (66/70). Fifty-six percent of the patients experienced mild-to-moderate lymphedema. Severe complications requiring surgical intervention were observed in 6 patients (5 bowel obstructions and 1 femoral head fracture). A review of the literature suggests that early carcinoma can be successfully treated by surgery alone. Taking into consideration the risk and benefits involved, postoperative radiotherapy is not recommended for most cases with cervical carcinoma with negative lymph nodes and positive parametrial involvement in the present form, despite excellent local control. However, no definite conclusion can be drawn from this retrospective analysis.

Introduction Carbon ion radiotherapy (CIRT) is a promising modality with excellent localization and significant biologic effects on tumors. Nevertheless, success depends primarily on accurate staging before radiotherapy. Surgical interventions should be avoided in patients considered for CIRT because they usually have multiple comorbidities. The aim of this study was to evaluate the effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in patients with non-small cell lung cancer before CIRT. Methods From April 2005 to December 2007, 49 patients with non-small cell lung cancer considered for CIRT with abnormal positron emission tomography-computed tomography (PET-CT) accumulations in the mediastinum and/or hilum were evaluated by EBUS-TBNA. The convex probe EBUS was used for EBUS-TBNA. Results There were 38 men and 11 women. Their mean age was 75.2 years (range: 55–87). Based on PET-CT, clinical staging was four with N1 disease, 42 with N2 disease, and three with N3 disease. By histology, 26 patients had adenocarcinoma, 19 had squamous cell carcinoma, and four had other histologies. All positive lymph nodes on PET-CT were aspirated (range: 1–5; average 2.55 lymph nodes/patient). EBUS-TBNA diagnosed 43 cases as N0 disease and as a result underwent CIRT. Forty of the 43 cases remained in stable condition without local recurrences (follow-up 6–46 months). The diagnostic accuracy of EBUS-TBNA for lymph node staging was 93.9%. Conclusions EBUS-TBNA offers accurate minimally invasive lymph node staging in patients who are candidates for CIRT. EBUS-TBNA can be safely performed with a high diagnostic accuracy before CIRT.

Charged particles can achieve better dose distribution and higher biological effectiveness compared to photon radiotherapy. Carbon ions are considered an optimal candidate for cancer treatment using particles. The National Institute of Radiological Sciences (NIRS) in Chiba, Japan was the first radiotherapy hospital dedicated for carbon ion treatments in the world. Since its establishment in 1994, the NIRS has pioneered this therapy with more than 69 clinical trials so far, and hundreds of ancillary projects in physics and radiobiology. In this review, we will discuss the evolution of carbon ion radiotherapy at the NIRS and some of the current and future projects in the field.

This study evaluated the efficacy of computed tomography (CT)-based three-dimensional (3D) dose-volume parameters of the rectum as predictor for late rectal complication (LRC) in cervical cancer patients treated with radiotherapy alone. Eighty-four patients treated with a combination of external radiotherapy and high-dose-rate intracavitary brachytherapy between January 2000 and December 2004 were retrospectively analyzed. Brachytherapy was prescribed with standard 2D planning. Patients underwent pelvic CT at brachytherapy. The external rectal wall was contoured on the CT images, and the minimum doses delivered to 0.1cc, 1cc, and 2cc of the most irradiated rectal volumes were calculated with dose-volume histograms. The International Commission of Radiation Units and Measurements (ICRU) rectal point dose was also calculated by conventional method. Total dose (external radiotherapy plus brachytherapy) to the rectum was transformed to the biologically equivalent dose in 2-Gy fractions with alpha/beta of 3 Gy (D(0.1cc), D(1cc), D(2cc) and D(ICRU)). The relationships between these dosimetric parameters and the incidence of LRC were analyzed. The 5-year overall actuarial rate of LRC was 26.4%. The values of D(0.1cc), D(1cc), and D(2cc) were significantly higher in patients with LRC than in those without (p < 0.001), but the difference in the values of D(ICRU) was not statistically significant (p = 0.10). The rate of LRC increased significantly with increasing D(0.1cc), D(1cc), and D(2cc) (p = 0.001). However, no positive dose-response relationship was observed between D(ICRU) and the rate of LRC (p = 0.42). The present study has suggested that CT-based 3D dose-volume parameters of the rectum may be effective for predicting LRC.

OBJECTIVE:: We evaluated changes in tumor volume in cases of sacral chordoma after carbon ion radiotherapy. METHODS:: Thirty-four patients with sacral chordoma underwent carbon ion radiotherapy between June 1996 and June 2003. We assessed 23 patients without previous surgery using T2-weighted magnetic resonance imaging. The tumor volume was calculated semiautomatically. RESULTS:: Two cases showed local recurrence. The median interval of this examination was 46 months. At the end of the treatment, the tumor showed an enlargement larger than 10% of its volume in 13 of the 23 cases, no change in 4 cases, and regression in 6 cases. At the last examination, 20 cases showed a reduction in tumor volume, and the median ratio, determined as the tumor volume at the last examination divided by that before the treatment, was 0.36. CONCLUSIONS:: An increase in tumor volume at the end of the treatment does not indicate the ineffectiveness of carbon ion radiotherapy.

Surgical resection is the standard treatment for stage I non-small cell lung cancer (NSCLC). However, elderly patients with NSCLC often suffer from other conditions, such as chronic obstructive pulmonary disease (COPD) or cardiovascular disease, and are not suitable candidates for surgery. Different modalities to treat stage I NSCLC have been developed, such as stereotactic radiotherapy (SRT), proton beam radiotherapy and carbon ion radiotherapy (CIRT). Between April 1999 and November 2003, we treated 129 patients with stage I NSCLC using CIRT. In this study, we focused on 28 patients aged 80 years and older who underwent CIRT, and analyzed the effectiveness of CIRT in treating their lung cancer and the impact on their activity of daily life (ADL). The 5-year local control rate for these patients was 95.8%, and the 5-year overall survival rate was 30.7%, but there were no patients who started home oxygen therapy or had decreased ADL. Our data demonstrate that CIRT was effective in treating elderly patients with stage I NSCLC.

Purpose To assess carbon ion beam dose variation due to bowel gas movement in pancreatic radiotherapy. Methods and Materials Ten pancreatic cancer inpatients were subject to diagnostic contrast-enhanced dynamic helical CT examination under breath-holding conditions, which included multiple-phase dynamic CT with arterial, venous, and delayed phases. The arterial–venous phase and arterial–delayed phase intervals were 35 and 145 s, respectively. A compensating bolus was designed to cover the target obtained at the arterial phase. Carbon ion dose distribution was calculated by applying the bolus to the CT data sets at the other two phases. Results Dose conformation to the clinical target volume was degraded by beam overshoot/undershoot due to bowel gas movement. The D95 for clinical target volume was degraded from 98.2% (range, 98.0–99.1%) of the prescribed dose to 94.7% (range, 88.0–99.0%) at 145 s. Excessive dosing to normal tissues varied among tissues and was, for example, 12.2 GyE/13.1 GyE (0 s/145 s) for the cord and 38.8 GyE/39.8 GyE (0 s/145 s) for the duodenum. The magnitude of beam overshoot/undershoot was particularly exacerbated from the anterior and left directions. Conclusions Bowel gas movement causes dosimetric variation to the target during treatment for radiotherapy. The effect of bowel gas movement varies with beam angle, with greatest influence on the anterior–posterior and left–right beams.

Purpose To determine the risk factors for persistent late genitourinary (GU) morbidity after carbon ion radiotherapy (C-ion RT) for prostate cancer. Methods and Materials Between April 2000 and November 2003, a Phase II study of 175 prostate cancer patients was performed to assess C-ion RT with a dose fractionation (66 Gray equivalent in 20 fractions) established from previous Phase I-II studies. The effects of the clinical and dosimetric parameters on the occurrence of persistent GU toxicity in 172 patients who survived for >18 months after C-ion RT were examined retrospectively. C-ion RT alone was performed for 33 low-risk patients, and 139 high-risk patients received C-ion RT combined with androgen deprivation therapy (ADT). Results Grade 1 and 2 persistent GU toxicities developed in 36 (21%) and 3 (2%) patients, respectively. The use of long-course ADT (≥24 months) and acute GU toxicity were associated with the occurrence of persistent toxicity by multivariate analysis ( p = 0.016 and p = 0.048, respectively), but short-course ADT ( p = 0.35). The 5-year actuarial complication rate of 80 patients undergoing long-course ADT was 31.1%; the corresponding rate for the 92 patients who received no ADT or short-course ADT was 22.2%. Conclusion Adverse effects with long-course ADT on persistent GU morbidity were observed in this study. Additional investigation is needed to identify suitable ADT administration according to risk groups, but long-course ADT should not be adopted for non–high-risk prostate cancer patients to reduce the GU toxicity rate with C-ion RT.

Purpose To prospectively assess patient quality of life (QOL) after carbon ion radiotherapy (C-ion RT) for prostate cancer, using established questionnaires. Methods and Material The subjects were 150 patients who underwent C-ion RT. Of these, 25 patients with low-risk prostate cancer received C-ion RT alone, whereas the remaining 125 patients with a high-risk tumor also received androgen deprivation therapy. Quality of life was assessed using the self-administered Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaire in all patients three times. In addition, the University of California-Los Angeles Prostate Cancer Index (UCLA-PCI) was conducted in the low-risk patients. Results The FACT–General (FACT-G) and FACT-P scores at 12 months after treatment averaged over all 150 patients showed no significant change compared with those before C-ion RT. In FACT-P subscales, emotional well-being increased significantly just after and 12 months after treatment. In contrast, physical well-being (PWB) and social/family well-being (S/FWB) decreased significantly at 12 months, whereas the prostate cancer subscale (PCS) decreased significantly just after treatment. Average scores for FACT-G, FACT-P, PWB, S/FWB, and PCS for the 125 patients receiving hormone therapy showed substantial detrimental changes at 12 months. In contrast, those of the 25 low-risk patients who had no hormone therapy showed no significant change. Similarly no significant change in the average of the UCLA-PCI scores in the low-risk patients was seen at 12 months. Conclusions Average QOL parameters reported by patients with localized prostate cancer treated with C-ion RT, in the absence of hormone therapy, showed no significant decrease 12 months after C-ion RT.

Osteosarcoma is a radioresistant tumor. There have been few reports on the effectiveness of radiotherapy for unresectable osteosarcoma using photon (X-ray) beams. Carbon ion beams have a unique physical advantage for avoiding irradiation of critical organs, and their biological effectiveness is higher than that of X-ray and proton beams. These specific characteristics are beneficial for the treatment of sarcomas. Carbon ion radiotherapy has thus been suggested as an effective local therapy for unresectable osteosarcoma of the trunk.

Carbon ions/Charged particles/Dose distribution/RBE/Clinical study. In 1994 a Phase I/II clinical study on carbon ion radiotherapy was begun at NIRS using HIMAC, which was then the world’s only heavy ion accelerator complex dedicated to medical use in a hospital environment. Among several types of ion species, we have chosen carbon ions for cancer therapy because they had the most optimal properties in terms of possessing, both physically and biologically, the most effective dose-localization in the body. The purpose of the clinical study was to investigate the efficacy of carbon ion radiotherapy against a variety of tumors as well as to develop effective techniques for delivering an efficient dose to the tumor. The RBE of carbon ions was estimated to be 2.0 to 3.0 along the SOBP for acute skin reactions. As of August 2006, a total of 2,867 patients had been entered into Phase I/II or Phase II studies and analyzed for toxicity and local tumor response. The results have shown that carbon ion radiotherapy has the potential ability to provide a sufficient dose to the tumor with acceptable morbidity in the surrounding normal tissues. Tumors that appear to respond favorably to carbon ions include locally advanced tumors and those with histologically non-squamous cell type of tumors such as adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, hepatoma, and bone/soft tissue sarcoma. By taking advantage of the biological and physical properties of high-LET radiation, the efficacy of treatment regimens with small fractions in short treatment times has been confirmed for almost all types of tumors in carbon ion radiotherapy.

Most cases of adenoid cystic carcinoma (ACC) of the tongue base are radioresistant, and are diagnosed in the advanced stage. Therefore, we evaluated the safety and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced ACC of the tongue base.Eighteen patients with ACC of the tongue base were treated with C-ion RT between May 2002 and April 2014. Seventeen patients had T4a disease and 1 patient had T2 disease before C-ion RT.The median follow-up period was 57 months (range, 10-132 months). The 5-year local control rate was 92%. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 72% and 44%, respectively. Regarding late reactions, 2 patients developed grade 3 mandible osteoradionecrosis, and 1 had grade 3 hemorrhage of the tongue base.C-ion RT was effective with acceptable toxicities for locally advanced ACC of the tongue base. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2122-E2126, 2016.

Purpose To compare carbon-ion beam dose distribution between passive and scanning radiation therapies for locally advanced pancreatic cancer. Materials and methods Thirteen pancreatic cancer patients were included in this study. Four types of treatment planning with respiratory gating were calculated for each patient: a four-field box with passive irradiation (Plan 1), scanning irradiation (Plan 2), a three-field (150°, 180° and 210°) protocol with passive irradiation (Plan 3), and scanning irradiation (Plan 4). The irradiation plans each delivered 55.2Gy (RBE) to the planning target volume (PTV) and were compared with respect to doses to the PTV and organs at risk (OARs). Results Plan 3 exceeded the dose assessment metrics to the spinal cord. Scanning irradiation plans (Plan 2 and, particularly, Plan 4) offered significantly reduced dosage to the stomach and the duodenum compared with passive irradiation. Conclusion Three-field oblique scanning irradiation for pancreatic cancer has the potential to reduce gastrointestinal exposure and influence of peristalsis on dose distribution.

Purpose Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. Methods and Materials A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. Results During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. Conclusion Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.

Our hospital is specialized for radiation therapy and has many information devices. Various job categories are working. When we implemented an EMR, we aimed to enforce ISMS by using IHE profiles. To solve the already existed system-related problems, we selected and use some profiles (EUA, PSA, ATNA and PAM). After implementation, we audited and then some findings were pointed out. These findings are being settled by the PDCA cycle. We also found that appropriate IHE profiles were effective in the building of ISMS.

In response to Japan’s first comprehensive 10-year strategy for cancer control and the aim to use carbon ion beams to irradiate cancer cells, the world’s first heavy ion accelerator designed for medical use, the Heavy IonMedical Accelerator in Chiba (HIMAC), was opened at the National Institute of Radiological Sciences (NIRS), Chiba, Japan, in 1994, and clinical trials on carbon ion radiation therapy (CIRT) began. From that time, and with the cooperation of experts throughout Japan, a clinical research network has been constructed, and in the past 20 years more than 9000 cancer patients have been treated with CIRT. In so doing, we have found particular success in the treatment of difficult-to-cure, intractable cancers for which other treatment options fall short, and our results using this cutting-edge method of radiation therapy have attracted attention throughout the world [1]. Based on the results of these clinical studies, in 2003 the Japanese government recognized CIRT as an ‘‘advanced medical technology’’ for the treatment of solid tumors, and from that year we have been able to offer treatment to patients for a variety of malignancies. In 2004, we succeeded in reducing the size and cost of ourCIRTequipment to one third that of the original, and the prototypewas placed atGunmaUniversitywith operation beginning in 2010. Thatmachine’s successor was developed at NIRS and then placed in Saga Prefecture’s Tosu City, beginning operation there in 2013. Research into treatmentmethodology has progressed as well: in 2011, a nextgeneration irradiation technique known as the scanning irradiation method was incorporated into the HIMAC at NIRS, and already more than 700 patients have received therapy by this method. Currently, a new system capable of the scanning irradiation method is being built in Kanagawa Prefecture that is planned to open by the end of 2015. Though the scanning method presents a difficulty when used in the treatment of respiration-mobile tumors/organs, at NIRSwehave successfully developed a fastmultiple scanning (‘‘rescanning’’) system that is capable of delivering treatment simultaneous with natural patient respiration, and clinical trials began in March 2015. In comparison with the passive beam method predominantly used at the HIMAC up until 2011, the scanning method offers further potential for miniaturizing the beam scattering and irradiation-field–forming equipment, and research is ongoing into this potential. Simultaneously, we have developed a small, lightweight, rotating gantry platform equipped with superconductive magnets, which is under construction and has a target date of early 2016 (Figure 1). In this article, we will review the experience and results at NIRS up until now, examine the future outlook of CIRT, and introduce our plans for future developments.

The detailed in vivo T1 -weighted contrasting abilities of nitroxyl contrast agents, which have been used as redox responsive contrast agents in several magnetic resonance-based imaging modalities, in mouse brain were investigated.Distribution and pharmacokinetics of five types of five-membered-ring nitroxyl radical compound were compared using T1 -weighted MRI.The blood-brain barrier (BBB) -impermeable 3-carboxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CxP) could not be distributed in the brain. The slightly lipophilic 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP) showed slight distribution only in the ventricle, but not in the medulla and cortex. The amphiphilic 3-methoxy-carbonyl-2,2,5,5-tetramethyl-pyrrolidine-N-oxyl (MCP) had good initial uniform distribution in the brain and showed typical 2-phase signal decay profiles. A brain-seeking nitroxyl probe, acetoxymethyl-2,2,5,5-tetramethyl-pyrrolidine-N-oxyl-3-carboxylate (CxP-AM), showed an accumulating phase, and then its accumulation was maintained in the medulla and ventricle regions, but not in the cortex. The lipophilic 4-(N-methyl piperidine)-2,2,5,5-tetramethylpyrroline-N-oxyl (23c) was well distributed in the cortex and medulla, but slightly in the ventricle, and showed relatively rapid linear signal decay.Nitroxyl contrast agents equipped with a suitable lipophilic substitution group could be BBB-permeable functional contrast agents. MR redox imaging, which can estimate not only the redox characteristics but also the detailed distribution of the contrast agents, is a good candidate for a theranostic tool. Magn Reson Med 76:935-945, 2016. © 2015 Wiley Periodicals, Inc.

Background The prognostic value of rectal invasion is still unclear in stage IVA cervical cancer. The objective of this study is to evaluate patient outcome and prognostic factors in stage IVA cervical cancer treated with radiation therapy. Methods A retrospective review of the medical records of patients treated with definitive photon radiation therapy for pathologically proven stage IVA cervical cancer between 1980 and 2010 was performed. Eligible patients for the present study were diagnosed with clinical stage IVA cervical cancer by cystoscopy or/and proctoscopy, and they received definitive radiation therapy consisting of a combination of external beam radiotherapy and high-dose-rate brachytherapy. All patients underwent CT scans of the abdomen and pelvis. Results Among the 67 stage IVA patients studied, 53 patients were stage IVA on the basis of bladder invasion, 7 according to rectal mucosal invasion, and 7 because of both bladder and rectal mucosal invasion. Median follow-up of all patients and surviving patients was 19 months (range, 2–235 months) and 114 months (range, 14–223 months), respectively. The 5-year local control (LC), disease-free survival (DFS), and overall survival (OS) rate were 55, 17, and 24 %, respectively. Rectal invasion had significant impact on DFS, but bladder invasion had the opposite effect (p = 0.00006 and 0.005, respectively). There were significant differences of LC, DFS and OS rates between patients with and without rectal invasion (p = 0.006, 0.00006 and 0.05, respectively). Conclusions Patients with stage IVA cervical cancer had poor prognosis, with 5-year survival of only 24 %. Furthermore, in stage IVA, rectal invasion might be a worse prognostic factor than bladder invasion.

The standard treatment for metastatic liver tumor from breast cancer is systemic medical treatment, and there is controversy regarding the value of local treatment. However, there are some exceptional cases that do benefit from local therapy. We describe the case of a 54-year-old woman with systemic therapy-resistant liver metastasis from breast cancer successfully treated with a single shot of 36-GyE carbon-ion radiotherapy and surviving more than 8 years without local recurrence. This case represents a good example of the usefulness and safety of carbon-ion radiotherapy, and who might benefit from local therapy.

A 55-year-old man, with a prior diagnosis of primary malignant melanoma of the esophagus, had undergone esophagectomy 6 years prior. During the postoperative follow-up, a flat tumor with black pigmentation, about 2 cm in diameter, was detected during upper gastrointestinal endoscopy. A pathological examination of the biopsy specimen showed a recurrent malignant melanoma. He underwent heavy ion radiotherapy for the tumor, and it disappeared after 6 months. Subsequently, a mediastinal lymph node metastasis was detected a year after radiotherapy. He received heavy ion radiotherapy for that tumor, and it was reduced in size a year after radiotherapy. At present, the patient is alive, 13 years after the initial radiotherapy. Although malignant melanoma is generally considered to be a radioresistant cancer, heavy ion radiotherapy led to a favorable outcome. This is the first reported case of heavy ion radiotherapy for treating the recurrence of a primary malignant melanoma of the esophagus.

Charged particle therapy is generally regarded as cutting-edge technology in oncology. Many proton therapy centres are active in the USA, Europe, and Asia, but only a few centres use heavy ions, even though these ions are much more effective than x-rays owing to the special radiobiological properties of densely ionising radiation. The National Institute of Radiological Sciences (NIRS) Chiba, Japan, has been treating cancer with high-energy carbon ions since 1994. So far, more than 8000 patients have had this treatment at NIRS, and the centre thus has by far the greatest experience in carbon ion treatment worldwide. A panel of radiation oncologists, radiobiologists, and medical physicists from the USA and Europe recently completed peer review of the carbon ion therapy at NIRS. The review panel had access to the latest developments in treatment planning and beam delivery and to all updated clinical data produced at NIRS. A detailed comparison with the most advanced results obtained with x-rays or protons in Europe and the USA was then possible. In addition to those tumours for which carbon ions are known to produce excellent results, such as bone and soft-tissue sarcoma of the skull base, head and neck, and pelvis, promising data were obtained for other tumours, such as locally recurrent rectal cancer and pancreatic cancer. The most serious impediment to the worldwide spread of heavy ion therapy centres is the high initial capital cost. The 20 years of clinical experience at NIRS can help guide strategic decisions on the design and construction of new heavy ion therapy centres.

Purpose: The aim of this study was to determine the risk factors for late gastrointestinal (GI) morbidity after hypofractionated carbon ion radiotherapy (C-ion RT) for prostate cancer. Methods and Materials: Between April 2000 and November 2003, a Phase II clinical trial of C-ion RT with a total dose of 66 GyE in 20 fractions was performed on 175 patients with prostate cancer, and the correlations of clinical and dosimetric parameters with the incidence of late GI toxicity in 172 patients who survived for more than 18 months were investigated. Results: Although no Grade 3–4 late morbidities of the rectum were observed, Grade 1 and 2 morbidities developed in 23 (13%) and 4 (2%) patients, respectively. Dose–volume histogram analysis revealed that the percentage of rectal volume receiving 50% of the prescribed dose (V50) was significantly higher in patients with rectal toxicity than without toxicity (13.2 ± 5.6% with toxicity; 11.4 ± 4.0% without toxicity, p = 0.046). Multivariate analysis demonstrated that the use of anticoagulation therapy ( p = 0.010) and rectal V50 ( p = 0.012) were significant risk factors for the occurrence of Grade 1–2 late GI toxicity. Conclusions: Although C-ion RT with hypofractionation yielded favorable results regarding late GI complication, dosimetric parameter was a very important factor in the occurrence of rectal bleeding after C-ion RT as well as photon beam RT. Our results provide useful information for physicians applying charged particle RT in the treatment of prostate cancer.