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Background: This study aimed to assess the safety and efficacy of carbon-ion radiotherapy (CIRT) for salvage of previously X-ray-irradiated (XRT) locally recurrent rectal cancer (LRRC). Methods: Between September 2005 and December 2017, 77 patients with LRRC were treated with CIRT re-irradiation. All the patients had received prior XRT with a median dose of 50.0 Gy (range 20-74 Gy), principally for neoadjuvant or adjuvant recurrence prophylaxis in 34 patients and for recurrence in 43 patients. The total CIRT dose of 70.4 Gy (RBE) (gray relative biologic effectiveness) was administered in 16 fixed fractions during 4 weeks (4.4 Gy [RBE] per fraction). Results: All the patients completed the scheduled treatment course. None of the patients received resection after CIRT. Acute grade 3 toxicities occurred for eight patients (10 %), including five grade 3 pelvic infections (2 involving pain and 1 involving neuropathy). Late grade 3 toxicities occurred for 16 patients (21 %): 13 with late grade 3 pelvic infections, 9 with gastrointestinal toxicity, 1 with skin toxicity, 2 with pain, and 4 with neuropathy. No grade 4+ toxicity was noted. The overall local control rates (infield + out-of-field recurrence) were 69 % at 3 years and 62 % at 5 years. In the planning target volume (PTV), the infield recurrence rates were 90 % and 87 % respectively. The control rates for regional recurrence were 85 % at 3 years and 81 % at 5 years. The median overall survival time was 47 months. The survival rates were 61 % at 3 years and 38 % at 5 years. Conclusion: Carbon-ion re-irradiation of previously X-ray-irradiated locally recurrent rectal cancer appears to be safe and effective, providing good local control and survival advantage without unacceptable morbidity.

In this study, the stopping-power ratios (SPRs) of mouthpiece materials were measured and the errors in the predicted SPRs based on conversion table values were further investigated. The SPRs of the five mouthpiece materials were predicted from their computed tomography (CT) numbers using a calibrated conversion table. Independently, the SPRs of the materials were measured from the Bragg peak shift of a carbon-ion beam passing through the materials. The errors in the SPRs of the materials were determined as the difference between the predicted and measured values. The measured SPRs (errors) of the Nipoflex 710™ and Bioplast™ ethylene-vinyl acetate copolymers (EVAs) were 0.997 (0.023) and 0.982 (0.007), respectively. The SPRs of the vinyl silicon impression material, light-curable resin, and bis-acrylic resin were 1.517 (0.134), 1.161 (0.068), and 1.26 (0.101), respectively. Among the five tested materials, the EVAs had the lowest SPR errors, indicating the highest human-tissue equivalency.

Background: Chordoma is a rare, locally invasive neoplasm of the axial skeleton. Complete resection is often difficult, especially for the upper-cervical (C1-2) spine. We evaluated the efficacy and safety of carbon-ion radiotherapy (CIRT) for unresectable C1-2 chordoma. Methods: Patients with C1-2 chordoma treated with definitive CIRT (60.8 Gy [RBE] in 16 fractions) were retrospectively analyzed. We evaluated OS, LC, PFS, and toxicity. Results: Nineteen eligible patients all completed the planned course of CIRT. With the median follow-up 68 months (range: 29-144), median OS was 126 months (range: 36-NA). Five-year OS, LC, and PFS were 68.4% (95% CI, 42.8%-84.4%), 75.2% (46.1%-90.0%), and 64.1% (36.3%-82.3%), respectively. Regarding acute toxicity of grade ≥3, there was only one grade 3 mucositis. Late toxicity included radiation-induced myelitis (grade 3 in 1 patient; 5.3%), and compression fractures (n = 5; 26.3%). Conclusions: High-dose CIRT is a promising treatment option for unresectable upper cervical chordoma.

Background: The efficacy of carbon-ion radiotherapy (C-ion RT) for lymph node (LN) oligo-recurrence has only been evaluated in limited single-center studies. We aimed to investigate the benefit of C-ion RT for LN oligo-recurrence in a large multi-center study. Methods: Patients who received C-ion RT between December 1996 and December 2015 at 4 participating facilities and who met the following eligibility criteria were included: (i) histological or clinical diagnosis of LN recurrence; (ii) controlled primary lesion; (iii) no recurrence other than LN; (iv) LN recurrence involved in a single lymphatic site; and (v) age ≥ 20 years. Results: A total of 323 patients were enrolled. Median follow-up period was 34 months for surviving patients. The most common dose fractionation of C-ion RT was 48.0 Gy (relative biological effectiveness) in 12 fractions. Forty-seven patients had a history of RT at the recurrent site. The 2-year local control (LC) and overall survival (OS) rates after C-ion RT were 85% and 63%, respectively. Only 1 patient developed grade-3 toxicity. Factors such as LN diameter, histology, and history of previous RT did not correlate with LC. Smaller diameters (< 30 mm) and numbers (≤ 3) of LN metastases as well as longer disease-free intervals post-primary therapy (≥ 16 months) were associated with significantly better OS. Conclusions: C-ion RT for LN oligo-recurrence appeared to be effective and safe. C-ion RT may provide a survival benefit to patients with LN oligo-recurrence, particularly to those with few LN metastases, smaller LN diameters, and longer disease-free intervals.

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.

The aim of this multi-institutional study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally advanced pancreatic cancer (LAPC).

For hypo-fractionated multi-ion therapy (HFMIT), the stochastic microdosimetric kinetic (SMK) model had been developed to estimate the biological effectiveness of radiation beams with wide linear energy transfer (LET) and dose ranges. The HFMIT will be applied to radioresistant tumors with oxygen-deficient regions. The response of cells to radiation is strongly dependent on the oxygen condition in addition to radiation type, LET and absorbed dose. This study presents an adaptation of the SMK model to account for oxygen-pressure dependent cell responses, and develops the oxygen-effect-incorporated stochastic microdosimetric kinetic (OSMK) model. In the model, following assumptions were made: the numbers of radiation-induced lesions (double-strand breaks and clustered DNA damages) are reduced due to lack of oxygen, and the numbers of oxygen-mediated lesions are reduced for radiation with high LET. The model parameters were determined by fitting survival data under aerobic and anoxic conditions for human salivary gland tumor cells and V79 cells exposed to helium-, carbon-, and neon-ion beams over the LET range of 18.5-654.0 keV/μm. The OSMK model provided good agreement with the experimental survival data of the cells with determination coefficients > 0.9. In terms of oxygen enhancement ratio, the OSMK model reproduced the experimental data behavior, including slight dependence on particle type at the same LET. The OSMK model was then implemented into the in-house treatment planning software for the HFMIT to validate its applicability in clinical practice. A treatment plan with helium- and neon-ion beams was made for a pancreatic cancer case assuming an oxygen-deficient region within the tumor. The biological optimization based on the OSMK model preferentially placed the neon-ion beam to the hypoxic region, while it placed both helium- and neon-ion beams to the surrounding normoxic region. The OSMK model offered the accuracy and usability required for hypoxia-based biological optimization in HFMIT treatment planning.

Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer.

To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival.

： To improve long-term local control and survival of locally recurrent rectal cancer, we have initiated a radiation dose-escalation trial using carbon ion beams. The purpose of this study is to evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients with locally recurrent rectal cancer. Between April 2001 and August 2012, 198 lesions at 189 patients were treated with C-ion RT. The dose was determined as 67.2 GyE and escalated to 70.4 GyE and 73.6 GyE. The local control rates in 197 lesions are 94 % at 3 years and 89 % at 5 years. Local control rate and survival rate at 5 years were 97 % at 73.6 GyE and 51 % at 73.6 GyE. In the literature, the reported 5-year survival rates for locally recurrent rectal cancer treated with resection were 20–40 %. Carbon ion radiotherapy seems to be a safe and effective modality in the management of locally recurrent rectal cancer, providing good local control and offering a survival advantage without acceptable morbidity. In this chapter, the treatment methods and the up-to-date outcomes of carbon ion radiotherapy (C-ion RT) for the recurrent rectal cancer at the NIRS are introduced.

Aim: The purpose of this study was to evaluate the role of FDG-PET regarding the indication of preoperative carbon-ion radiotherapy (CIRT) for pancreatic cancer patients. PATIENTS AND METHODS: Patients with resectable pancreatic cancer underwent preoperative CIRT. The impact of baseline SUVmax on prognosis for patients was assessed by analyzing correlations with distant metastasis-free survival (DMFS) and overall survival (OS). RESULTS: Out of 21 patients, local recurrence was observed in no patient and distant metastasis was found in 13 patients (62%). 1-year DMFS and OS in low-SUVmax group were significantly higher than those in high-SUVmax group (91% vs. 20% and 91% vs. 56%). SUVmax was significantly correlated with DMFS and OS. CONCLUSION: Our data indicated a significant correlation between SUVmax and DMFS. FDG-PET might be useful for determining the indication of preoperative short-course CIRT for patients with resectable pancreatic cancer.

： Pancreatic cancer is the fifth leading cause of cancer death and is considered to be one of the most lethal cancers in Japan. Complete surgical resection is the only curative treatment. Even if curative resection is performed, the disease usually recurs, and 5-year survival rates are less than 20 %. Chemotherapy or chemoradiotherapy is selected as a standard treatment for unresectable pancreatic cancer. However, since pancreatic cancer is often resistant to chemotherapy and radiotherapy, the local control and survival rates are very low. We conducted a phase I/II clinical trial using carbon ion radiotherapy (C-ion RT) for patients with operable and locally advanced pancreatic cancer. This was delivered preoperatively in 8 fractions over 2 weeks, was well tolerated, and resulted in excellent local control and survival rates. C-ion RT for patients with locally advanced pancreatic cancer was also well tolerated, even when concomitantly administered with the highest dose of gemcitabine (1,000 mg/m2), and likewise resulted in a good survival rate. We discuss current treatment methods and the results of C-ion RT for pancreatic cancer at the National Institute of Radiological Sciences.

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.

A trial of carbon ion radiotherapy (C-ion RT) for hepatocellular carcinoma (HCC) was first conducted in April 1995 at the National Institute of Radiological Sciences (NIRS) in Japan. A total of 193 patients with HCC were enrolled in this clinical trial. In the first and second phase I/II clinical trials, dose escalation studies were carried out in incremental steps of 10%, resulting in the confirmation of both the safety and efficacy of short-course regimens of 12, 8, and 4 fractions. Based on the results, a phase II clinical study with fixed fractionation, that is, 52.8 GyE/4 fractions, was performed. A total of 47 patients were treated during this phase II study, which resulted in low toxicity and attained a high local control rate (96%) for 5 years after treatment. The last clinical study was conducted from April 2003 to August 2005, with a more hypofractionated regimen of 2 fractions/2 days, in which 36 patients were safely treated within a dose escalation range from 32.0 GyE to 38.8 GyE. The 2-fraction therapy protocol is continuing under the license of Highly Advanced Medical Technology. There have been no therapy-related deaths and no severe adverse events. We conclude that, because of the low toxicity and high local control rate, C-ion RT is a promising new, radical, and minimally invasive therapeutic option for HCC., 2nd NIRS-ETOILE Joint Symposium on Carbon Ion Therapy

The large intestine starts at the ascending colon, which is connected to the small bowel, and ends at the rectum, which extends from the sacral promontory to the anal canal. In 2008, approximately 43,000 patients died of colorectal cancer in Japan which is the third most common cause of cancer deaths, after lung and stomach cancers. Approximately 100,000 patients were diagnosed with colorectal cancer in 2004, thus making it the second most common type of cancer after stomach cancer. The analysis of the post-operative recurrence rates of colorectal cancer indicates a higher rate for rectal cancer than colon cancer. When compared by the site of recurrence, rectal cancer had a more than three times higher local recurrence rate than colon cancer. With the recent advances in surgical techniques and procedures, the pelvic recurrence rate of rectal cancer has been decreasing, however the post-operative recurrence rate is still 5% to 20% today. Surgical resection is the first choice for locally recurrent rectal cancer, although total pelvic extenteration or another highly invasive procedure is often required. In many cases, locally recurrent rectal cancers are not completely resectable so generally surgical resections are not selected. The comparison of resection rates by the type of tumors shows that the resection rates were in the range of 40% to 50% for liver metastases and 20% to 40% for lung metastases, whereas the rate was 10% to 40% for locally recurrent colorectal cancers (Table 1)1,2) Curative resection of thesetumors will lead to a survival rate similar to those for other types of recurrences and metastases. Radiation therapy is often indicated for unresectable cases of locally recurrent rectal cancer; most of the past studies on conventional x-ray radiotherapy reported a 12-month median survival and a 10% 3-year overall survival. The use of adjuvant chemotherapy elevated the local control rate up to around 20%, which is far from satisfactory. Heavy charged particle beams have been shown to exert potent anti-tumor effects against radioresistant adenocarcinomas. To improve both the long-term local control and survival of locally recurrentrectal cancer, we have initiated a radiation dose-escalation trial using heavy charged particles.

OBJECTIVES: To assess the efficacy and toxicity of radical chemoradiotherapy for patients with synchronous head and neck squamous cell carcinoma (HNSCC) and esophageal cancer (EC). METHODS: Thirty-four patients with synchronous HNSCC and EC were treated mainly with radical chemoradiotherapy at the same time. Median external radiation dose for HNSCC and EC was 70 Gy (range, 60-70.5 Gy), except for 2 patients with tongue cancer, who underwent brachytherapy and 60 Gy (range, 45-70 Gy), respectively. Thirty-one patients were treated with concurrent chemoradiotherapy with cisplatin and/or 5-fluorouracil or TS-1 (oral anticancer agent that combines tegafur, a metabolically activated prodrug of 5-fluorouracil, with 5-chloro-2, 4-dihydoroxypyridine, and potassium oxonate). RESULTS: Thirty-three patients completed the intended treatment. The response rate was 94%, with 26 complete responses (76%) and 6 partial responses (18%). At a median follow-up of 17.3 months, 2-year rates of overall survival, cause-specific survival, and disease-free survival were 44%, 52%, and 33%, respectively. Initial failure patterns were local failure in 14 patients (63%), regional progression in 3 patients (13%), and distant metastasis in 6 patients (27%). The most common acute toxicity was myelosuppression, with 8 patients experiencing grade 3-4 toxicity. Three patients experienced grade 3 mucositis and pharyngitis. No patients experienced late morbidity of grade 3 or higher. CONCLUSIONS: Definitive chemoradiotherapy for patients with synchronous HNSCC and EC is feasible with a low mortality rate and acceptable morbidity.

The number of deaths from pancreatic cancer in Japan exceeds 26,000 per year, and the number is increasing every year1. Pancreatic cancer is the fifth leading cause of cancer death and it is considered to be one of the most lethal cancers in Japan. Complete surgical resection is the only curative treatment. However, only a small percentage of patients (10-20%) are candidates for surgical resection because of local progression or metastatic spread at the time of diagnosis2, 3. Even if a curative resection is performed, the disease usually recurs and 5-year survival rates are less than 20% 4, 5. Chemotherapy or chemoradiotherapy is selected as a standard treatment for unresectable pancreatic cancer. However, since pancreatic cancer is often resistant to chemotherapy or radiotherapy, the local control rate is very low. Recently, along with the development of new anticancer agents, the irradiation techniques have greatly progressed following the introduction of highly advanced radiotherapy. However, the outcome from therapy is still not satisfactory, with the median survival being approximately 10 months6, 7. We started phase I/II clinical trial for pre-operative carbon ion radiotherapy (CIRT) with 16 fractions in 4 weeks for resectable pancreatic cancer in 2000 (Figure 1). The purpose of this treatment was to reduce the risk of postoperative local recurrence, which accounts for approximately 50% of total recurrences. We established the tolerance and effectiveness of preoperative CIRT and performed a clinical trial aimed at shortening the fraction size to 8 fractions in 2 weeks beginning in 2003 (Protocol 0203). In addition, we started phase I/II clinical trial for patients with locally advanced pancreatic cancer and showed that the treatment was safe and provided excellent local control rates. Accordingly, we are currently performing a clinical trial of using carbon ion radiotherapy combined with gemcitabine (Protocol 0513)., 2nd NIRS-ETOILE Joint Symposium on Carbon Ion Therapy

The treatment of hepatocellular carcinoma (HCC) associated with underlying chronic liver diseases should include every possible effort to maintain optimal liver function. Charged particle therapy using proton and carbon ion beams provides a sharper and more focused irradiation to the target region of the liver than conventional X-ray radiotherapy. It therefore reduces the risk of tratment-related liver damage. A series of four clinical studies of carbon ion radiotherapy for the treatment of HCC were conducted at the National Institute of Radiological Sciences from June 1995 to Augst 2005. These studies determined the optimal doses for radiotherapy for HCC. We also contributed to reducing the number of irradiation sessions, and achieved a shorter treatment period. The treatment schedule was simplified from 15 fractions over five weeks to two fractions for two days. The local control rates for the carbon ion radiotherapy were around 90% across various tumor sizes, tumor locations, and fractionations schedule. In most of the patients, the liver function showed no or a minor deterioration. Heavy charged particle therapy, which provides a safe and powerful therapeutic modality for tumors of all sizes, is an excellent choice for the treatment of HCC. It can be used effectively in conjunction with other approaches available in multidisciplinary disease management.

In June 1994, the world's first clinical center offering carbon ion radiotherapy opened at the National Institute of Radiological Science (NIRS), Japan. Among several types of ion species, carbon ions were chosen for cancer therapy because they were judged to have the most optimal properties in terms of superior physical and biological characteristics. As of March 2010, 5,196 patients have been registered for carbon ion radiotherapy. Clinical results have shown that carbon ion radiotherapy has the potential to provide a sufficient radiation dose to the tumor, while having acceptable morbidity in the surrounding normal tissues. Tumors that appear to respond favorably to carbon ions include locally advanced tumors as well as histologically non-squamous cell tumor types such as adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, hepatoma, and bone/soft tissue sarcoma. By taking advantage of the unique properties of carbon ions, treatment with small fractions within a short treatment period has been successfully carried out for a variety of tumors. This means that carbon ion radiotherapy can offer treatment for larger numbers of patients than is possible with other modalities over the same time period.

Purpose: To evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients with locally recurrent rectal cancer. Patients and Methods: We conducted a phase I/II dose escalation study of carbon ion radiotherapy . One hundred patients with 105 sites of locally recurrent cancer receiving carbon ion radiotherapy were analyzed. Forty-eight relapses originated in the presacral region, 28 in the pelvic sidewalls, 16 in the perineal region and 8 in the colorectal anastomosis. The total dose ranged from 67.2 to 73.6 gray equivalent (GyE) and was administered in 16 fixed fractions over 4 weeks (4.2to 4.6 GyE/fraction). Results: None of 75 patients treated with the highest total dose of 73.6 GyE experienced National Cancer Institute-Common Toxicity Criteria grade 3 to 5 acute reactions. The local control rate in patients treated with 73.6 GyE in the present study was 97% at one year and 92% at 3 years. Dose escalation was then halted at this leval. The median survival time in patients treated with 73.6 GyE was 54 months (range, 7 to 65 months), and the 1-and 3-year overall survival rates were 71% at 3 years and 39% at 5 years, respectively. Conclusion: Carbon ion radiotherapy seems to be a safe and effective modality in the management of locally recurrent rectal cancer, providing good local control and offering a survival advantage without unacceptable morbidity., II NIRS-CNAO Joint Symposium on Hadrontherapy

The number of deaths from pancreatic cancer in Japan exceeds 26,000 per year, and the number is increasing every year1. Pancreatic cancer is the fifth leading cause of cancer death and it is considered to be one of the most lethal cancers in Japan. Complete surgical resection is the only curative treatment. However, only a small percentage of patients (10-20%) are candidates for surgical resection because of local progression or metastatic spread at the time of diagnosis2, 3. Even if a curative resection is performed, the disease usually recurs and 5-year survival rates are less than 20% 4, 5. Chemotherapy or chemoradiotherapy is selected as a standard treatment for unresectable pancreatic cancer. However, since pancreatic cancer is often resistant to chemotherapy or radiotherapy, the local control rate is very low. Recently, along with the development of new anticancer agents, the irradiation techniques have greatly progressed following the introduction of highly advanced radiotherapy. However, the outcome from therapy is still not satisfactory, with the median survival being approximately 10 months6, 7. We started phase I/II clinical trial for pre-operative carbon ion radiotherapy (CIRT) with 16 fractions in 4 weeks for resectable pancreatic cancer in 2000 (Figure 1). The purpose of this treatment was to reduce the risk of postoperative local recurrence, which accounts for approximately 50% of total recurrences. We established the tolerance and effectiveness of preoperative CIRT and performed a clinical trial aimed at shortening the fraction size to 8 fractions in 2 weeks beginning in 2003 (Protocol 0203). In addition, we started phase I/II clinical trial for patients with locally advanced pancreatic cancer and showed that the treatment was safe and provided excellent local control rates. Accordingly, we are currently performing a clinical trial of using carbon ion radiotherapy combined with gemcitabine (Protocol 0513)., New Frontiers in Cancer Treatment

Adenocarcinoma of the pancreas continues to be a significant source of cancer mortality in Japan, resulting in approximately 19,000 deaths a year. It is the fifth leading cause of cancer-related deaths in Japan, with a less than 5% 5-year expected survival rate. About 70-75% of patients with pancreas cancer present with locally advanced disease or distant metastases and have a median survival time of only 6 months. For unresectable pancreas cancer, the median survival time with external beam radiation (EBRT) was better than with surgical bypass or stents alone. The median survival of EBRT alone was 4 to 7 months. The median survival with combined EBRT and chemotherapy for locally unresectable tumor was 8 to 10 months, better than with EBRT alone. Local failure of these combined therapies was still 26 to 48%. On the other hand, surgery with curative intent is undertaken in 15-20% of patients. Even after resection, the predicted 5-year survival rates are still less than 20%. Local recurrence in the pancreatic bed is seen in 50% of the patients undergoing presumed curative resection. We examined the effect of carbon ion therapy in terms of reducing the rate of local recurrence in patients with locally advanced adenocarcinoma of the pancreas or undergoing resection for adenocarcinoma of the pancreas.

Carbon Ion Therapy of Rectal and Pancreatic Cancer Introduction: Pancreatic cancer is the fifth leading cause of cancer death and is considered to be one of the most lethal cancers in Japan. Chemotherapy and/or chemoradiotherapy are usually selected as standard treatment for unresectable pancreatic cancer. However, since pancreatic cancer is often resistant to chemotherapy and radiotherapy, the local control rate is very low. We initiated a phase I/II clinical trial of carbon-ion radiotherapy (C-ion RT) combined with gemcitabine in patients with locally advanced pancreatic cancer. Materials and Methods: The eligibility criteria for this study were as follows: locally advanced pancreatic cancer that involved the celiac trunk or superior mesenteric artery without distant metastasis. All patients had histologically or cytologically proven pancreatic adenocarcinoma. The radiation fractions were fixed at 12 fractions over three weeks, and the doses of gemcitabine and radiation were gradually increased. First, the radiation dose was fixed at 43.2 GyE/8 fractions, and the gemcitabine dose was increased from 400 to 700 to 1,000 mg/m2. Subsequently, the gemcitabine dose was fixed at 1,000 mg/m2 and the radiation dose was increased from 43.2 GyE to 55.2 GyE in 5% increments. Gemcitabine was administered for three consecutive weeks, once a week. Results: Seventy-five patients were registered from April 2007 through February 2012. Of these patients, 71 were clinically eligible for the study. Four patients were ineligible and excluded from the analyses due to liver metastases that became obvious before the administration of C-ion RT (n=3) and the inadequacy of histological confirmation (n=1). The median age was 63 (range: 39-74) years. The performance status was 0 in 10 patients, 1 in 48 patients and 2 in one patient. The clinical stage according to the UICC was stage III in 53 cases and stage IV in 18 cases. The most common grade 3 acute toxicities were hematological toxicity (51%) and anorexia (8%). Dose limiting toxicity (DLT) developed as an early adverse event in three of the 71 patients: grade 3 cholangitis in one patient and grade 4 leukopenia in two patients, indicating a low incidence. With regard to late toxicities, one patient treated at the 50.4 GyE dose level developed a grade 3 gastric ulcer 10 months after undergoing CIRT; however, the patient recovered with conservative management. No other serious adverse events were observed. The combination therapies with full-dose gemcitabine (1,000 mg/m2) were not associated with an increased incidence of adverse events with dose escalation. The median survival time was 21 months. Among all patients, the two-year local control rate and two-year overall survival rate were 74% and 39%, respectively. In the high-dose group (n=47), in which the patients were irradiated with at least 45.6 GyE, the two-year local control rate and two-year overall survival rate were 86% and 49%, respectively. Conclusions: C-ion RT is well tolerable even when concomitantly administered with the highest dose of gemcitabine (1,000 mg/m2). Long-term survival or a radical cure can be expected following further dose escalation or the administration of maintenance chemotherapy., The Cancer Symposium: Advanced Radiation Oncology Treatment Strategies with Photon, Proton, and Carbon Ion Radiation

American Society for Therapeutic Radiology and Oncology ASTRO's 54th Annual Meeting

Purpose/Objective(s): To evaluate the effectiveness and usefulness ofcarbon ion radiation therapy (CIRT) in patients with lymph node recur-rence, we analyzed our treatment results with various primary sites. \nMaterials/Methods: Patient's eligibility of CIRT for lymph node recur-rence in principle were, 1) lymph node recurrence after primary treatment,2) no other metastasis has been observed, 3) ECOG PS 0-2, 4) at least 5-mm gap between the recurrent lesion and radiosensitive organs, includinggastrointestinal tract and bladder, and 5) Irradiated field not exceeding 15cm. In some cases, Gore-Tex made spacer had been inserted surgicallybefore CIRT to make a gap between surrounding radiosensitive tissue. AsCIRT technique, all sites were irradiated using 3-D conformal planningsystem with 2 to 4 portals, with respiratory gating if necessary. In targetdelineation, involved node was defined as GTV, prophylactic lymph nodearea was defined as CTV, and CTV + 5 mm (excluding GI) was defined as PTV. Treatment was performed 4 times a week, up to a total dose of 48GyE / 12 fractions / 3 weeks in principle. \nResults: From December 1996 to February 2012, 189 cases with 233 siteswere treated. Patient' age ranged from 32 to 87 with a median of 65, with141 males and 92 females. The primary sites were lung in 68, rectum in 44,pancreas in 12, uterine cervix and body in 11, colon in 8, stomach and esophagus in 5, renal pelvis in 4 and others in 21. The tumors were histologically classified as follows: 160 with adenocarcinoma, 37 squa-mous cell carcinoma, 12 with transitional cell carcinoma, and 24 with others. The sites of recurrent lymph nodes were 92 in chest, 69 in abdomen, 59 in pelvis and 13 in neck. The radiation doses were 30-38.4GyE in 10, 40-45.6GyE in 18, 48GyE in 106, 50.2-57.6GyE in 84, 60- 64GyE in 9 and 70.4-73.6GyE in 6 cases. Among them, 23 sites were previously irradiated. The follow up period ranged from 1 month to 9 years7 months with a median of 1 year 6 months. No acute grade 3 or higheradverse toxicities have been observed. Late adverse events were observed in 1 case, who developed duodenum bleeding at re-irradiate site. Tumorprogressions were recognized at irradiated sites in 18 (8%), regional in 34(15%), whereas distant sites in 128 (55%). At the time of analysis. 115 patients had died, including 99 of the malignancies and 16 of intercurrent diseases. Survival rates were calculated at 204 sites followed for more than6 months from the completion of the treatment or followed to the death. The overall survival rates of entire group were 77.3% in 1 year, 52.8% in 2year, 42.5% in 3 year and 29.0% in 4 year, respectively (median survivaltime: 2 year and 2 months). The overall 2 year survival rates of lung and rectal cancer were 45.4% and 42.6%, respectively. \nConclusions: CIRT for lymph node recurrence from various malignanciesmight be promising to have favorable local control with acceptable toxicities, although not affecting to reduce distant metastases., ASTRO's 54th Annual Meeting

51st Annual Meeting of Particle Therapy Co-Operrative Group

Purpose/Objective The aim of this study was to evaluate the role of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) in the indication of preoperative carbon ion radiotherapy for the patients with resectable pancreatic cancer. Materials and Methods The patients with resectable pancreatic cancer underwent preoperative short course carbon ion radiotherapy (CIRT) in our institution. On the PET-CT before CIRT, the tumor was contoured and the maximum standardized uptake value (SUVmax) was calculated. The SUVmax was compared between two groups, patients with and without distant recurrence after CIRT. The low-SUVmax and the high-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The impact of the SUVmax on the prognosis for patients was assessed by analyzing the correlations between the SUVmax and the distant metastasis free survival (DMFS) and overall survival (OS). In addition, the analysis was performed by following factors; age, carbohydrate antigen 19-9, tumor volume, and clinical stage. Results Twenty-one patients were included in this study. Sixteen of 21 patients underwent surgery. For the entire population, local recurrence was observed in no patient and distant metastasis in 13 patients (62%). The median SUVmax was 4.3 (range, 2.2-8.2). DMFS of the low-SUVmax group and the high- SUVmax group were 91% and 20% for 1 year and 71% and 0% for 3 year, respectively (p4.3 was the only risk factor for distant recurrence in the univariate analysis. Conclusions Our data indicated statistically significant correlation between SUVmax and DMFS. FDG-PET is considered to be useful to determine the indication of preoperative short course CIRT for the patients with resectable pancreatic cancer., ESTRO 31

New Frontiers in Cancer Treatment: A Focus on Photon and Carbon Ion Radiation Therapy

The large intestine starts at the ascending colon, which is connected to the small bowel, and ends at the rectum, which extends from the sacral promontory to the anal canal. In 2008, approximately 43,000 patients died of colorectal cancer in Japan which is the third most common cause of cancer deaths, after lung and stomach cancers. Approximately 100,000 patients were diagnosed with colorectal cancer in 2004, thus making it the second most common type of cancer after stomach cancer. The analysis of the post-operative recurrence rates of colorectal cancer indicates a higher rate for rectal cancer than colon cancer. When compared by the site of recurrence, rectal cancer had a more than three times higher local recurrence rate than colon cancer. With the recent advances in surgical techniques and procedures, the pelvic recurrence rate of rectal cancer has been decreasing, however the post-operative recurrence rate is still 5% to 20% today. Surgical resection is the first choice for locally recurrent rectal cancer, although total pelvic extenteration or another highly invasive procedure is often required. In many cases, locally recurrent rectal cancers are not completely resectable so generally surgical resections are not selected. The comparison of resection rates by the type of tumors shows that the resection rates were in the range of 40% to 50% for liver metastases and 20% to 40% for lung metastases, whereas the rate was 10% to 40% for locally recurrent colorectal cancers (Table 1)1,2) Curative resection of thesetumors will lead to a survival rate similar to those for other types of recurrences and metastases. Radiation therapy is often indicated for unresectable cases of locally recurrent rectal cancer; most of the past studies on conventional x-ray radiotherapy reported a 12-month median survival and a 10% 3-year overall survival. The use of adjuvant chemotherapy elevated the local control rate up to around 20%, which is far from satisfactory. Heavy charged particle beams have been shown to exert potent anti-tumor effects against radioresistant adenocarcinomas. To improve both the long-term local control and survival of locally recurrentrectal cancer, we have initiated a radiation dose-escalation trial using heavy charged particles., New Frontiers in Cancer Treatment

The large intestine starts at the ascending colon, which is connected to the small bowel, and ends at the rectum, which extends from the sacral promontory to the anal canal. In 2008, approximately 43,000 patients died of colorectal cancer in Japan which is the third most common cause of cancer deaths, after lung and stomach cancers. Approximately 100,000 patients were diagnosed with colorectal cancer in 2004, thus making it the second most common type of cancer after stomach cancer. The analysis of the post-operative recurrence rates of colorectal cancer indicates a higher rate for rectal cancer than colon cancer. When compared by the site of recurrence, rectal cancer had a more than three times higher local recurrence rate than colon cancer. With the recent advances in surgical techniques and procedures, the pelvic recurrence rate of rectal cancer has been decreasing, however the post-operative recurrence rate is still 5% to 20% today. Surgical resection is the first choice for locally recurrent rectal cancer, although total pelvic extenteration or another highly invasive procedure is often required. In many cases, locally recurrent rectal cancers are not completely resectable so generally surgical resections are not selected. The comparison of resection rates by the type of tumors shows that the resection rates were in the range of 40% to 50% for liver metastases and 20% to 40% for lung metastases, whereas the rate was 10% to 40% for locally recurrent colorectal cancers (Table 1)1,2) Curative resection of thesetumors will lead to a survival rate similar to those for other types of recurrences and metastases. Radiation therapy is often indicated for unresectable cases of locally recurrent rectal cancer; most of the past studies on conventional x-ray radiotherapy reported a 12-month median survival and a 10% 3-year overall survival. The use of adjuvant chemotherapy elevated the local control rate up to around 20%, which is far from satisfactory. Heavy charged particle beams have been shown to exert potent anti-tumor effects against radioresistant adenocarcinomas. To improve both the long-term local control and survival of locally recurrentrectal cancer, we have initiated a radiation dose-escalation trial using heavy charged particles. \nThe number of deaths from pancreatic cancer in Japan exceeds 26,000 per year, and the number is increasing every year1. Pancreatic cancer is the fifth leading cause of cancer death and it is considered to be one of the most lethal cancers in Japan. Complete surgical resection is the only curative treatment. However, only a small percentage of patients (10-20%) are candidates for surgical resection because of local progression or metastatic spread at the time of diagnosis2, 3. Even if a curative resection is performed, the disease usually recurs and 5-year survival rates are less than 20% 4, 5. Chemotherapy or chemoradiotherapy is selected as a standard treatment for unresectable pancreatic cancer. However, since pancreatic cancer is often resistant to chemotherapy or radiotherapy, the local control rate is very low. Recently, along with the development of new anticancer agents, the irradiation techniques have greatly progressed following the introduction of highly advanced radiotherapy. However, the outcome from therapy is still not satisfactory, with the median survival being approximately 10 months6, 7. We started phase I/II clinical trial for pre-operative carbon ion radiotherapy (CIRT) with 16 fractions in 4 weeks for resectable pancreatic cancer in 2000 (Figure 1). The purpose of this treatment was to reduce the risk of postoperative local recurrence, which accounts for approximately 50% of total recurrences. We established the tolerance and effectiveness of preoperative CIRT and performed a clinical trial aimed at shortening the fraction size to 8 fractions in 2 weeks beginning in 2003 (Protocol 0203). In addition, we started phase I/II clinical trial for patients with locally advanced pancreatic cancer and showed that the treatment was safe and provided excellent local control rates. Accordingly, we are currently performing a clinical trial of using carbon ion radiotherapy combined with gemcitabine (Protocol 0513)., NIRS-KFSHRC Joint Symposium on Carbon Ion Radiotherapy and Radiation Emergency Medicine

Purpose: Since 1995, carbon ion radiotherapy (C-ion RT) has been performed for treatment of HCC, and clinical trials were initiated at the National Institute of Radiological Science (NIRS). This study was conducted to evaluate the efficacy and safety of C-ion RT in elderly patients with hepatocellular carcinoma (HCC). \nMaterials and methods: Sixty-four patients with HCC, including 24 elderly (aged >70 years) patients, were treated with C-ion RT of 52.8GyE in 4 fractions between April 2000 and March 2003. Baseline characterstics, local control/survival rates, and adverse events were compared between elderly and non-elderly patients (≤70 years old vs. >70 years old). \nResults: There were no significant differences in UICC clinical stage and Child-Pugh grade between the 2 groups. No hepatic failure resulting from the therapy and no treatment-related death occurred. The cumulative overall survival rates in the elderly group were 58.3% at 3 years and 29.2% at 5 years, which was equivalent to the non-elderly group. The local control rates after both 3 and 5 years were 95.8% and 92.4% in the elderly group and the non-elderly group, respectively. There were no significant differences between the 2 groups. \nConclusions: Short-course C-ion RT for the patients with HCC appears to be safe and effective in elderly patients, as well as non-elderly patients., The 22nd Congress of the Asian Pacific Association for the Study of the Liver

The large intestine starts at the ascending colon, which is connected to the small bowel, and ends at the rectum, which extends from the sacral promontory to the anal canal. In 2008, approximately 43,000 patients died of colorectal cancer in Japan which is the third most common cause of cancer deaths, after lung and stomach cancers. Approximately 100,000 patients were diagnosed with colorectal cancer in 2004, thus making it the second most common type of cancer after stomach cancer. The analysis of the post-operative recurrence rates of colorectal cancer indicates a higher rate for rectal cancer than colon cancer. When compared by the site of recurrence, rectal cancer had a more than three times higher local recurrence rate than colon cancer. With the recent advances in surgical techniques and procedures, the pelvic recurrence rate of rectal cancer has been decreasing, however the post-operative recurrence rate is still 5% to 20% today. Surgical resection is the first choice for locally recurrent rectal cancer, although total pelvic extenteration or another highly invasive procedure is often required. In many cases, locally recurrent rectal cancers are not completely resectable so generally surgical resections are not selected. The comparison of resection rates by the type of tumors shows that the resection rates were in the range of 40% to 50% for liver metastases and 20% to 40% for lung metastases, whereas the rate was 10% to 40% for locally recurrent colorectal cancers (Table 1)1,2) Curative resection of thesetumors will lead to a survival rate similar to those for other types of recurrences and metastases. Radiation therapy is often indicated for unresectable cases of locally recurrent rectal cancer; most of the past studies on conventional x-ray radiotherapy reported a 12-month median survival and a 10% 3-year overall survival. The use of adjuvant chemotherapy elevated the local control rate up to around 20%, which is far from satisfactory. Heavy charged particle beams have been shown to exert potent anti-tumor effects against radioresistant adenocarcinomas. To improve both the long-term local control and survival of locally recurrentrectal cancer, we have initiated a radiation dose-escalation trial using heavy charged particles., 2nd NIRS-ETOILE Joint Symposium on Carbon Ion Therapy

EANM'11 - Annual Congress of the European Association of Nuclear Medicine

Background/aims: To compare the efficacy and safety of the short-course carbon ion radiotherapy (C-ion RT) for hepatocellular carcinoma (HCC) in terms of tumor histological differentiation. Methods: The study consisted of 63 patients undergoing C-ion RT of 52.8 GyE in 4 fractions between April 2000 and March 2003. Eligibility criteria were as follows: biopsy-proven HCC; recurrent or residual tumor after other ineffective treatments or no indication for any other treatment; no tumor thrombosis of main trunk of portal vein; no other viable lesion outside the planning target volume; no prior radiotherapy for target tumors; hepatic disorder of Child-Pugh classification A or B; ECOG performance status of 0-2; no other active cancer; and digestive tract not in contact with clinical target volume. Maximum tumor diameter was 4.0cm (range 1.2-12.0 cm). Four were well differentiated tumor, 2 were well to moderately-differentiated, 51 were moderately differentiated, 4 were moderately to poorly-differentiated, and 2 were poorly differentiated. The total dose delivered was 52.8 GyE in 4 fractions for 1 week. The dose per fraction was 13.2 GyE. Results: The 5-year local control rates were 100.0% in the well differentiated group, 96.0% in the moderately differentiated group, 83.3% in the poorly differentiated group, respectively. The 5-year overall survival and cause-specific survival rates were 33.3% and 33.3% in the well differentiated group, 23.4% and 32.8% in the moderately differentiated group, and 25.0% and 25.0% in the poorly differentiated group, respectively. There were no significant differences (P = 0.710, P = 0.977, respectively). Further, there were no significant differences in late liver toxicity, and no hepatic failure resulting from the therapy and no treatment-related death occurred. Conclusions: Excellent local control was obtained independent of tumor histological differentiation. Short-course C-ion RT appears to be an effective and safe treatment modality for all histological type of HCC. Outcomes after short-course carbon ion radiotherapy for patients with hepatocellular carcinoma according to tumor size., The 21st Conference of the Asian Pacific Association for the Study of the Liver

Purpose: Since 1995, carbon ion radiotherapy (C-ion RT) has been performed for treatment of hepatocellular carcinoma (HCC), and clinical trials were initiated at the National Institute of Radiological Science. Even though the early detection has progressed, HCC that exceeds 5cm exists in no small way. This time, we compared the treatment results in terms of tumor size. Materials and methods: The study consisted of 69 patients undergoing C-ion RT of 52.8GyE in four fractions between April 2000 and March 2003. We divided into two groups (more than 5cm or not) and compared local control, survival, and adverse events between the two groups. Results: The enrolled patients consisted of 52 males and 17 females. Median age was 69 years (range, 37-84). Median maximum tumor diameter was 4.0cm, 5cm or less was 53 examples, 5-10cm was 14 examples, and 10-15cm was 2 examples. When the patients divided into two groups according to tumor size (≤5cm vs. >5cm), there were no significant differences in late liver toxicity. No hepatic failure resulting from the therapy and no treatment-related death occurred. The 5-year local tumor control rates were 94% in two groups. The overall 5-year survival rate was 36% (≤5cm) and 13% (>5cm). There were no significant differences between the two groups (P = 0.162). Conclusions: The 5-year local control rate was 94% in two groups (≤5cm vs. >5cm) and the effectiveness of the C-ion RT as the local treatment was shown. Short-course C-ion RT appears to be an effective and safe therapeutic option for HCC regardless of tumor size., The 21st Conference of the Asian Pacific Association for the Study of the Liver

Purpose Cu-62labeled diacetyl-bis (N(4)-methylthiosemicarbaone) (Cu-62-ATSM) is a well-knownhypoxic imaging PET tracer. The purpose of this study was to delineate thedifferences in intratumoral uptake and tracer distribution of Cu-62-ATSM andF-18 FDG in patients with pancreas cancer. The comparison of two tracers wasdone before and after carbon ion radiotherapy, and the relationship of traceruptake and patients prognosis was also investigated. Mehod Two male and twofemale (mean age, 62.5 y, range 52-69 y) with pancreas cancer underwent bothCu-62-ATSM and FDG PET/CT before the initiation of carbon ion radiotherapy(CIRT), and the set of PET/CT studies was done one month after termination ofCIRT. Two whole-body PET/CT scanners, Biograph-16 (Siemens) and Aquiduo(Toshiba) were used for data acquisition. Cu-62-ATSM and FDG were administratedapproximately 740 MBq and 370 MBq, respectively. Tumor uptake of each tracerwas analyzed semi-quantitatively by tumor to normal tissue ratio (TNR) forCu-62-ATSM and by standardized absorption value (SUV) for FDG. Result Cu-62-ATSMuptake didnt correlate with FDG uptake before CIRT, but it inverselycorrelated with FDG after CIRT because FDG uptake tended to decrease in allcases. Correlation coefficient of tumor uptake between Cu-62-ATSM and FDGbefore and after CIRT was 0.022 and -0.965, respectively. Average Cu-62-ATSMand FDG uptake before CIRT were 2.9 TNR (range 1.4-3.6 TNR) and 6.7 SUV (range2.9-10.6 SUV), and decreased to 2.7 TNR (range 1.2-4.7 TNR) and 3.8 SUV (range2.6-4.6) after CIRT, respectively. In three out of four patients before CIRTshowed high Cu-62-ATSM uptake that might reflect the trend of them beinghypoxic. A patient showed increase of Cu-62-ATSM uptake after CIRT, but FDGuptake of the same patient didnt increase and almost stable after CIRT. It mightindicate that change of Cu-62-ATSM uptake didnt necessarily correspond tochange of FDG uptake after radiotherapy. Only one patient died after CIRT, andhis Cu-62-ATSM and FDG uptake before therapy were not the highest uptake withinall patients, but both of them were relatively high. Conclusion Cu-62-ATSM andFDG didnt correlate each other before CIRT in pancreas cancer. The change ofCu-62-ATSM uptake didnt necessarily correspond to change of FDG uptake afterCIRT. Cu-62-ATSM and FDG uptake of a patient who died after CIRT were not thehighest uptake, but were relatively high., The 2010 EANM Congress

The objective of this paper is to present a summary of a clinical study on carbon ion radiotherapy (C-ion RT) for hepatocellular carcinoma (HCC) conducted from April 1995 to August 2005 at the Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, in Japan. A total of 193 patients with HCC were enrolled in the clinical trial of carbon ion beams. In the first and second phase I/II clinical trials, dose escalation experiments were carried out in incremental steps of 10%, resulting in the confirmation of both the safety and efficacy of short-course regimens of 12, 8 and 4 fractions. Based on the results, a phase II clinical study with fixed fractionation, that is, 52.8 GyE/4 fractions, was performed. A total of 47 patients were treated during this phase II study, which resulted in low toxicity and attained a high local control rate (96%) for 5 years after treatment. The last clinical study was conducted from April 2003 to August 2005 with a more hypofractionated regimen of 2 fractions/2 days, in which 36 patients were safely treated within a dose escalation range from 32.0 GyE to 38.8 GyE. The 2-fraction therapy protocol is continuing under the license of Highly Advanced Medical Technology. There have been no therapy-related deaths and no severe adverse events. We can conclude that, because of the low toxicity and high local control rate, C-ion RT has a promising potential as a new, radical, and minimally invasive therapeutic option for HCC., The 4th Japanese-European Joint Symposium on Ion Cancer Therapy

Purpose: To evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients with locally recurrent rectal cancer. Patients and Methods: We conducted a phase I/II dose escalation study of carbon ion radiotherapy. One hundred twenty-nine patients with 134 sites of locally recurrent cancer receiving carbon ion radiotherapy were analyzed. Fifty-eight relapses originated in the presacral region, 45 in the pelvic sidewalls, 20 in the perineal region and 9 in the colorectal anastomosis. The total dose ranged from 67.2 to 73.6 gray equivalent (GyE) and was administered in 16 fixed fractions over 4 weeks (4.2 to 4.6 GyE/fraction). Results: None of the 104 lesions treated with the highest total dose of 73.6 GyE experienced National Cancer Institute - Common Toxicity Criteria grade 3 to 5 acute reactions. The local control rate in patients treated with 73.6 GyE in the present study was 98% at one year and 95% at 5 years. The dose escalation was then halted at this level. The median survival in the patients treated with 73.6 GyE was 54 months (range, 7 to 82 months), and the overall survival rates were 74% at 3 years and 45% at 5 years, respectively. Conclusion: Carbon ion radiotherapy seems to be a safe and effective modality in the management of locally recurrent rectal cancer, providing good local control and offering a survival advantage without unacceptable, The 4th Japanese-European Joint Symposium on Ion Cancer Therapy

Propose: Carbon ion radiotherapy (CIRT) offers the potential advantages of improved dose localization and enhanced biological effect. We examined the effect of CIRT in terms of reducing the rate of local recurrence in patients with locally advanced adenocarcinoma of the pancreas. Methods: Between April 2003 and February 2007, 46 patients with locally advanced pancreas cancer were eligible for this analysis. Patients eligible for study entry had histologically or cytologically confirmed with invasive ductal adenocarcinoma of the pancreas. Eligibility criteria were confirmation of invasive ductal carcinoma by CT findings, age of 80 years or younger, ECOG performance score 0, 1, or 2, and adequate hepatic, renal and cardiopulmonary function sufficient for undergoing surgery. The criteria of the CT findings for non-resectability of the tumor included tumor encasement of the celiac trunk and/or superior mesenteric artery. CIRT was given once daily, 4 days a week, for fixed 12 fractions in 3 weeks. The dose was set at 38.4GyE and escalated to 52.8GyE at 5% increments. Toxicity on organs such as the skin, digestive tract and liver was assessed according to the NCI-CTC classifications. Tumor response was defined by the RECIST scoring system as the maximum tumor response observed during the first 6 months after the initiation of CIRT. Local recurrence was defined in terms of lesions occurring in the tumor bed. Results: All patients completed the scheduled treatment course. Seven grade 3 acute and two grade 3 late toxicities were observed. Six of 7 grade 3 acute toxicities were anorexia and one was cholangitis. Complete response (CR) was observed in one lesion, partial response (PR) in 7,stable disease (SD) in 37, and progressive disease (PD) was observed in one lesion. The local control rates at one year in the 46 analyzed patients and in the patients receiving 45.6GyE or more were 85% and 95% respectively. The one year overall survival rate were 44% at all patients, and 47% at higher than 45.6GyE respectively. Conclusion: CIRT for locally advanced pancreas cancer seems to be safe and effective, however we could not get sufficient survival benefit. We started a phase I/II clinical trial of gemcitabine combined with CIRT for patients with locally advanced pancreas cancer from April 2007. At present we are trying to give 1000mg/m2 combined with 48GyE of carbon ion. All patients completed the scheduled treatment course with no major toxicity. This trial is still going., 第49回粒子線治療世界会議

Purpose: To evaluate the safety and efficacy of the short-course carbon ion radiotherapy (C-ion RT) of 52.8 GyE in 4 fractions for hepatocellular carcinoma (HCC). Methods: Sixty-nine patients were enrolled. Eligibility criteria were as follows: biopsy-proven HCC; recurrent or residual tumor after other ineffective treatments or no indication for any other treatment; no tumor thrombosis of the portal main branch; no other viable lesion outside the planning target volume; no prior radiotherapy for target tumors; hepatic disorder of Child-Pugh classification A or B; Karnofsky performance status of 60-100; no other active cancer; and digestive tract not in contact with clinical target volume. The total dose delivered was 52.8 GyE in 4 fractions for 1 week. The dose per fraction was 13.2 GyE. Results: No hepatic failure resulting from the therapy and no treatment-related death occurred. In 91% and 90% of patients, the Child-Pugh score did not increase by more than 1 point in the early and late phase, respectively. The 5-year overall survival and local control rates were 31% and 94%, respectively. In patients with suitable stage for hepatic resection, that is, a single lesion of 3 to 5 cm in diameter and Child-Pugh classification A liver function, overall survival rate was 69% at 5 years. Conclusions: In most of patients with HCC, short-course C-ion RT does not reduce liver function. It seems to be a minimally invasive and effective therapy for HCC., 第49回粒子線治療世界会議

Adenocarcinoma of the pancreas continues to be a significant source of cancer mortality in Japan, resulting in approximately 19,000 deaths a year. It is the fifth leading cause of cancer-related deaths in Japan, with a less than 5% 5-year expected survival rate. About 70-75% of patients with pancreas cancer present with locally advanced disease or distant metastases and have a median survival time of only 6 months. For unresectable pancreas cancer, the median survival time with external beam radiation (EBRT) was better than with surgical bypass or stents alone. The median survival OF EBRT alone was 4 to 7 months. The median survival with combined EBRT and chemotherapy for locally unresectable tumor was 8 to 10 months, better than with EBRT alone. Local failure of these combined therapies was still 26 to 48%. On the other hand, surgery with curative intent is undertaken in 15-20% of patients. Even after resection, the predicted 5-year survival rates are still less than 20%. Local recurrence in the pancreatic bed is seen in 50% of the patients undergoing presumed curative resection. We examined the effect of carbon ion therapy in terms of reducing the rate of local recurrence in patients with locally advanced adenocarcinoma of the pancreas or undergoing resection for adenocarcinoma of the pancreas., II NIRS-CNAO Joint Symposium on Hadrontherapy

Purpose: We examined the maximum-tolerated dose and effect of carbon ion therapy alone for locally advanced pancreas cancer. Patients and Methods: Between April 2003 and February 2007, 46 patients with locally advanced pancreas cancer were eligible for this analysis. Patients eligible for study entry had histologically or cytologically confirmed with pancreas ductal adenocarcinoma. Carbon ion therapy was given once daily, 4 days a week, for fixed 12 fractions in 3 weeks. The dose was set at 38.4 GyE and escalated to 52.8 GyE at 5% increments. Results: Seven grade 3 acute and two grade 3 late toxicities were observed. Six of 7 grade 3 acute toxicities were anorexia. The maximum acute reaction of the grade 3 was observed in two-thirds of the patients (67%) on the 52.8 GyE. CR was observed in one lesion, PR in 7, SD in 37. The local control rate at one year in the all patients and in the patients receiving 45.6 GyE or more was 76% and 95% and the overall survival rate was 44% and 73%, respectively. Conclusion: Carbon ion radiotherapy seems to be a safe and effective modality in the management of locally advanced pancreas cancer, providing good local control and offering a survival advantage without unacceptable morbidity., 40ｔｈ Anniversary Meeting of APA and JPS