Search

Background/Aim: The curative treatment for solitary fibrous tumors (SFTs) consists of surgery. However, surgery for SFTs in the skull base is difficult due to the anatomy and curative surgery may not be possible. Carbon-ion radiotherapy (C-ion RT) might be useful in the treatment of inoperable SFTs in the skull base because of its biological and physical nature. This study presents the clinical outcomes of C-ion RT for an inoperable SFT of the skull base. Case Report: A 68-year-old female patient experienced hoarseness, deafness on the right side, right facial nerve paralysis, and dysphagia. Magnetic resonance imaging revealed a tumor located in the right cerebello-pontine angle with destruction of the petrous bone, and immunohistochemical studies of the biopsy specimen showed a grade 2 SFT. Firstly, the patient underwent tumor embolization and surgery. However, 5 months after surgery, magnetic resonance imaging revealed regrowth of residual tumor. Subsequently, the patient was referred to our hospital for C-ion RT because curative surgery was unsuitable. The patient received 64 Gy (relative biological effectiveness) of C-ion RT in 16 fractions. Two years after C-ion RT, the tumor showed a partial response. The patient was still alive at the last follow-up without evidence of local recurrence, distant metastasis, or late toxicities. Conclusion: These findings suggest that C-ion RT is a suitable treatment option for inoperable SFTs of the skull base.

Carbon ion beams constitute the primary delivery method of heavy ion radiotherapy. It offers improved dose distribution, and enables concentration of dose within target volumes with minimal extraneous exposure of normal tissue, while delivering superior biological effect in comparison with photon and proton technologies. Here, we review the application of this technology to various gastrointestinal cancers.

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

Purpose: Carbon ion beams have several physical and biological advantages compared with conventional radiation for cancer therapy. The objective of this study is to evaluate the safety and effectiveness of 2-fraction carbon ion radiation therapy (CIRT) in patients with hepatocellular carcinoma (HCC). Methods and Materials: Between December 2008 and March 2013, 57 patients with localized HCC were treated with CIRT at a total dose of 45 Gy (relative biological effectiveness) in 2 fractions and retrospectively analyzed after long-term observation. The main endpoints of this study were treatment-related toxicity and local tumor control. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Changes in the Child-Pugh score from before to after CIRT were also examined to evaluate hepatic toxicity. Local control was defined as no progression of the irradiated lesion according to the modified Response Evaluation Criteria in Solid Tumors. Results: The median age of the patients was 75 years (range, 49-89 years). Of these patients, 41 had a newly diagnosed lesion, and 16 had residual or recurrent lesions after previous treatments.

The aim of this study was to evaluate the efficacy and safety of carbon-ion radiation therapy for nonsquamous cell carcinomas of the oral cavity in a multicenter study.

To evaluate the safety and efficacy of carbon-ion radiotherapy (CIRT) for cholangiocarcinoma via a multicenter retrospective study. Clinical data were collected from patients with cholangiocarcinoma who had received CIRT at one of four treating institutions in Japan. Of 56 eligible patients, none received surgery for cholangiocarcinoma before or after CIRT. The primary endpoint was overall survival (OS). Based on the tumor site, the 56 cases were categorized as intrahepatic cholangiocarcinoma (IHC) (n=27) or perihilar cholangiocarcinoma (PHC) (n=29). In all patients, the median tumor size was 37 (range, 15‒110) mm, and the most commonly prescribed dose was 76 Gy (relative biological effectiveness) in 20 fractions. The median survival was 14.8 (range, 2.1-129.2) months, and the 1- and 2-year OS rates were 69.7% and 40.9%, respectively. The median survival times of the patients with IHC and those with PHC were 23.8 and 12.6 months, respectively. Both univariate and multivariate analyses revealed that cholangitis pre-CIRT and Child‒Pugh class B were significant prognostic factors for an unfavorable OS. Of four patients who died of liver failure, one with IHC was suspected to have radiation-induced liver disease because of newly developed ascites, and died at 4.3 months post-CIRT. Grade 3 CIRT-related bile duct stenosis was observed in one IHC case. No other CIRT-related severe adverse events, including gastrointestinal events, were observed. These results suggest that CIRT yields relatively favorable treatment outcomes, especially for patients with IHC, and acceptable toxicities were observed in patients with cholangiocarcinoma who did not receive surgery.

Introduction We previously demonstrated the efficacy and utility of carbon-ion radiation therapy (CIRT), finding acceptable toxicity with preserved speech and wallowing function in the setting of locally advanced tongue carcinoma. The 5-year local control rate and overall survival rate were 92.0% and 72%, respectively, among 18 patients with locally advanced adenoid cystic carcinoma of the tongue base. However, osteoradionecrosis (ORN) of the mandibular bone remains a serious adverse event for patients receiving CIRT. The incidence of grade 3 mandibular ORN was 11.1%. Further study found that the volume of maxilla receiving more than 50 Gy (relative biological effectiveness [RBE]) across 16 fractions (maxilla V50 Gy [RBE] [mL]) and the presence of teeth within the planning target volume (PTV) were significant independent risk factors for ORN. As such, reducing the volume irradiated with high dose is one key way to reduce the risk of mandibular ORN. Spacers are widely used to prevent ORN in brachytherapy for tongue ncer. However, with regard to external photon radiation therapy (RT) for tongue arcinoma,there have been no reports on the utility of spacers focused on revention of ORN, perhaps because of the dose distribution inherent to photon RT. CIRT offers improved lateral dose distribution with minimal target exit dose and thereby may benefit from the employment of a spacer-including mouthpiece. In this technical report, we introduce and evaluate the utility of a spacer-including mouthpiece with the aim of producing reduced mandible V50 for the treatment of tongue carcinoma.

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

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

Purpose: The QA team of the Japan carbon‐ion radiation oncology study group (J‐CROS) was organized in 2015 to enhance confidence in the accuracy of clinical dosimetry and ensure that the facility QA procedures are adequate. The team conducted onsite dosimetry audits in all the carbon‐ion radiation therapy centers in Japan. Materials and Methods: A special phantom was fabricated for the onsite dosimetry audit. Target volumes such as the GTV, CTV, and PTV were contoured to the obtained CT images, and two plans with different isocenter depths were created. The dose at the isocenter was measured by an ionization chamber, in the onsite audit and compared with the calculated dose. Results: For all the centers, the average of the percentage ratio between the measured and calculated doses (measured/calculated) was 0.5% (−2.7% to +2.6%) and the standard deviation, 1.7%. In all the centers, the beams were within the set tolerance level of 3%. Conclusions: The audit demonstrated that the dose at a single point in the water phantom was within tolerance, but it is a big step to say that all doses are correct. In addition, this external dosimetry audit encouraged centers to improve the quality of their dosimetry systems.

BACKGROUND: This multi-institutional retrospective study focused on the clinical outcome of carbon-ion radiotherapy (C-ion RT) for non-squamous cell malignant tumors of the nasopharynx. METHODS: The Japan Carbon-ion Radiation Oncology Study Group collected and analyzed data for 43 patients with non-squamous cell malignant tumors of the nasopharynx treated with C-ion RT at four institutions in Japan. RESULTS: Twenty-nine patients had adenoid cystic carcinomas, seven had malignant melanomas, three had adenocarcinomas, two had mucoepidermoid carcinomas, and two had other pathologies. Twenty-six of the 43 patients (61%) had T4 tumors. The most common dose-fractionation schedule was 64 Gy (relative biological effectiveness) in 16 fractions. The median follow-up period was 30 months. The 2-year local control (LC) and overall survival (OS) rates were 88% and 84%, respectively. For late toxicity, one patient developed grade 4 optic nerve disorder and two developed grade 5 pharyngeal hemorrhage. Actual incidence of grade 3 or higher late adverse events was 19%, and included cranial nerve dysfunction, jaw bone necrosis, central nervous system necrosis, and ear inflammation. CONCLUSIONS: C-ion RT provided good LC and OS rates with acceptable toxicity for treatment of non-squamous cell malignant tumors of the nasopharynx.

Prognosis is usually grim for those who cannot receive resection with liver metastasis from colorectal cancer (CRC). Radiation therapy can be an option for those unsuitable for resection, and carbon-ion radiotherapy (CIRT) would be expected higher effective and less toxic than X-ray due to its physio-biological characteristics. The objective of this study is to identify the optimal dose of single fraction CIRT for colorectal cancer liver metastasis. Thirty-one patients with liver metastasis from CRC were enrolled. Twenty-nine patients received a single-fraction CIRT, escalating dose from 36 Gy (RBE) in 5 to 10% increments until unacceptable incidence of dose-limiting toxicity is observed. Dose-limiting toxicity was defined as grade ≥ 3 acute toxicity attributed to radiotherapy. The prescribed doses were: 36 Gy (RBE) (3 cases), 40 (2), 44 (4), 46 (6), 48 (3), 53 (8), and 58 (3). Dose-limiting toxicity was not observed but late grade 3 liver toxicity due to biliary obstruction was observed in 2 patients at 53 Gy (RBE). Both cases had lesions close to the hepatic portal region, and therefore dose was escalated to 58 Gy (RBE) limited to peripheral lesions. Three-year actuarial overall survival rate of all 29 patients was 78%, and median survival time was 65 months. Local control improved significantly at ≥53 Gy (RBE), with 3-year actuarial local control rate of 82%, compared to 28% in lower doses. Treatment for CRC liver metastasis with single-fraction CIRT appeared to be safe up to 58Gy (RBE) as long as the central hepatic portal region is avoided. This article is protected by copyright. All rights reserved.

AIM: Evaluation of the therapeutic efficacy of carbon-ion radiation therapy for isolated lymph node recurrence following curative resection of esophageal cancer. MATERIALS AND METHODS: Ten cases with lymph node recurrence after esophageal cancer surgery were treated with carbon-ion radiation therapy. A total of 48.0 Gy [relative biologic effectiveness (RBE)] was delivered over 3 weeks with a daily dose of 4.0 Gy (RBE). RESULTS: The median follow-up duration was 27.1 months (range=3-92.0 months) after carbon-ion radiation therapy. The local control rates at 2, 3 and 5 years were 92.4%. The overall survival rates at 2, 3 and 5 years were 70.0%, 58.3% and 21.9%. The median survival period was 45.3 months after carbon-ion radiation therapy. There were no toxicities of grade 3 or higher. CONCLUSION: Carbon-ion radiation therapy may be a safe and effective treatment option for isolated lymph node recurrence after radical surgery for esophageal cancer.

The long-term oncologic outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12/16-fraction CIRT at our institution outside of clinical trials. The outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7-16.5) years; 9 of these patients were inoperable because of comorbidities or advanced-stage disease. The diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In four of five patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney, or solitary kidney pre-CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although one case of grade 4 dermatitis was observed, there were no other grade 3 or higher non-renal adverse events. The local control rate, and disease-free, cancer-specific, and overall survival rates at 5- years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long-term follow-up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre-CIRT, and yielding favorable treatment outcomes, even in inoperable cases. This article is protected by copyright. All rights reserved.

It has been known that heart disease—such as myocardial infarction (MI), cardiac hypertrophy, or heart failure—alters the molecular structure and function of the gap junction, which can lead to an abnormal heart rhythm. Radiation has been shown to modulate intercellular communication in the skin and lungs by increasing connexin43 (Cx43) expression. Understanding how Cx43 upregulation is induced in a diseased heart can help provide a new perspective to radiation therapy for arrhythmias. In a recent study with rabbits after MI, carbon ions were accelerated to 290 MeV/u and extracted in the air; a biologically (cell kill) uniform 6-cm spread-out Bragg peak beam was generated, and beam tissue depth was set to 30 mm with energy degraders to the depth position. Targeted heavy ion irradiation (THIR) with 15 Gy to the left ventricle increased Cx43 expression, improved conductivity, decreased the spatial heterogeneity of repolarization, and reduced the vulnerability of rabbit hearts to ventricular arrhythmias after MI. In clinically normal rabbits, THIR (>10 Gy) caused a significant dose-dependent increase of Cx43 protein and messenger RNA 2 weeks after irradiation. The left (irradiated) and right (non-irradiated) ventricles exhibited circumferential upregulation of Cx43 lasting for at least 1 year. There were no significant changes in electrocardiograms and echocardiograms, indicating no apparent injury for 1 year. A single exposure of 135 MeV/u THIR with 15 Gy to a dog heart attenuated vulnerability to ventricular arrhythmia after the induction of MI for at least 1 year through the modulation of Cx43 expression. This long-lasting remodeling effect on gap junctions may lay the groundwork to novel therapies against life-threatening ventricular arrhythmias in structural heart disease. To date, there have been few investigations into the effects of carbon-ion irradiation on electrophysiological properties in the human heart. Patients with mediastinum cancer were investigated for 5 years after treatment that included irradiation to the heart, and investigators found that carbon-ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction. Its practical application in non–cancer treatment, such as in arrhythmia treatment, is highly anticipated.

Carbon ion radiotherapy is known for its high-precision dose distribution and high biological effectiveness. We evaluated the results of carbon ion radiotherapy in 128 patients with unresectable localized axial soft tissue sarcoma at a single institution.The patients’ median age was 54 years, and the median follow-up period was 49.4 (range 6.4-146.4) months. The median tumor volume was 356 cm3. The 5-year local control, overall survival, and disease-free survival rates were 65%, 46%, and 39%,respectively. In the univariate analysis, tumor volume, local control, and incidences of metastases were significantly related to overall survival. In the multivariate analysis,tumor volume and local control were significantly related to overall survival. We did not find any factors related to local control. Five patients required surgical intervention because of adverse events in the bones. Carbon ion radiotherapy may be a treatment option for unresectable axial soft tissue sarcoma.

Anti-tumor immunity modulates the local effects of radiation therapy. High mobility group box 1 (HMGB1) plays a pivotal role in activating antigen-specific T-cell responses. Here, we examined the relationship between linear energy transfer (LET) and HMGB1 release. We assessed the proportions of KYSE-70, HeLa and SiHa cells surviving after carbon-ion (C-ion) beam irradiation with different LET values, using a clonogenic assay. The D10, the dose at which 10% of cells survived, was calculated using a linear-quadratic model. HMGB1 levels in the culture supernatants of C-ion beam-irradiated tumor cells were assessed by enzyme-linked immunosorbent assay. The D10 doses for 13 keV/μm of C-ion irradiation in KYSE-70, HeLa and SiHa cells were 2.8, 3.9 and 4.1 Gy, respectively, whereas those for 70 keV/μm C-ion irradiation were 1.4, 1.9 and 2.3 Gy, respectively. We found that 70 keV/μm of C-ion irradiation significantly increased HMGB1 levels in the culture supernatants of all cell lines 72 h after irradiation compared with non-irradiated controls. Furthermore, 70 keV/μm of C-ion irradiation significantly increased HMGB1 levels in the culture supernatants of all cell lines 72 h after irradiation compared with 13 keV/μm. The results suggest that HMGB1 release from several cancer cell lines increases with increased LET.

Background: Unresectable pediatric osteosarcoma has poor outcomes with conventional treatments. Results: Twenty-six patients aged 11-20 years (median 16) had inoperable osteosarcoma of the trunk (24 pelvic, 1 mediastinal and 1 paravertebral) without any other lesion at initial examination. There were 22 primary, 1 locally recurrent and 3 metastatic cases. Median CIRT dose was 70.4 Gy RBE (relative biological effectiveness) delivered in 16 fractions. Median follow-up was 32.7 months. Overall survival was 50.0% and 41.7% at 3 and 5 years, respectively. Ten patients survived for more than 5 years (range 5-20.7 years). Local control was 69.9% and 62.9% at 3 and 5 years, respectively and progression-free survival was 34.6% at 3 and 5 years. Only largest tumor diameter correlated with 5-year overall survival and local control. There were 4 grade 3-4 CIRT-related late toxicities, 1 case of bone fracture and no treatment-related mortalities. All patients (except 1) were able to ambulate after CIRT. Conclusions: CIRT was safe and efficacious in the treatment of inoperable pediatric osteosarcoma with improved local control and overall survival compared to conventional treatments. Methods: We retrospectively reviewed the records of pediatric and adolescent patients who received carbon ion radiotherapy (CIRT) for inoperable osteosarcoma between 1996 and 2014.

Intrathoracic recurrence after carbon-ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer-related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re-irradiation with carbon-ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon-ion radiotherapy who were treated with re-irradiation with carbon-ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy-three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon-ion radiotherapy was 52.8Gy (relative biological effectiveness) and the median dose of re-irradiation was 66.0Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow-up period after re-irradiation was 18months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2-year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re-irradiation with carbon-ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re-irradiation with carbon-ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors.

A retrospective multicenter study was conducted to assess the clinical outcomes of carbon-ion radiotherapy for head and neck malignancies (Japan Carbon-Ion Radiation Oncology Study Group [J-CROS] study: 1402 HN). We evaluated the safety and efficacy of carbon-ion radiotherapy in patients with major salivary gland carcinoma. Sixty-nine patients treated with carbon-ion radiotherapy at 4 Japanese institutions were analyzed. Thirty-three patients (48%) had adenoid cystic carcinomas, 10 (14%) had mucoepidermoid carcinomas, and 26 (38%) had other disease types. Three patients (4%) had T1 disease, 8 (12%) had T2, 25 (36%) had T3, and 33 (48%) had T4. The median radiation dose was 64 Gy (relative biological effectiveness) in 16 fractions. The median gross tumor volume was 27 mL. The median follow-up period was 32.7 months. The 3-year local control rate and overall survival rate were 81% and 94%, respectively. Regarding acute toxicities, 7 patients had grade 3 mucositis and 7 had grade 3 dermatitis. Regarding late toxicities, 1 patient had grade 3 dysphagia and 1 had a grade 3 brain abscess. No grade 4 or worse late reactions were observed. In conclusion, definitive carbon-ion radiotherapy was effective with acceptable toxicity for major salivary gland carcinomas.

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

Carbon-ion radiation therapy (CIRT) for advanced non–small-cell lung cancer (NSCLC) has not been well studied to date. This paper aimed to analyze a retrospective multicenter survey for detecting problems with the use of CIRT for Stage II and III NSCLC (7th UICC TNM Staging System). Inclusion was restricted to patients with Stage II and III NSCLC who received CIRT from November 2003 to December 2014. We gathered the data from three CIRT operating centers on July 2015. Patients with radiotherapy history, patients with cancers other than lung cancer, and those receiving palliative therapies were excluded. The patient characteristics, prescribed dose/fraction, survival rates, and adverse effects were analyzed. The total number of patients was 64 (male: 49, female: 15). Of these, 53 patients were medically inoperable. The median age was 76 years (range 46–91), and the median follow-up period was 18.5 months (range 3.2–121.5). The clinical staging consisted of 10 Stage IIA, 30 Stage IIB, 23 Stage IIIA and 1 Stage IIIB. The median prescribed dose was 72.0 Gy (RBE) (range 52.8–72.0) in 16 fractions (range 4–16). The 2-year overall survival, progression-free survival, and local control rates were 62.2% [confidence interval (CI): 47.5–76.9], 42.3% (CI: 28.8–55.8) and 81.8% (CI: 69.9–94.0), respectively. There were no higher than Grade 2 adverse effects observed. CIRT for inoperable Stage II and III NSCLC could be implemented without severe adverse effects, but the clinical staging (including lymph node status) was inhomogeneous. In addition, the prescribed dose and fractionation were not standardized. Further data accumulation and a multiple centers prospective trial for evaluating clinical stage–based results are required.