A retrospective multicenter study of carbon-ion radiotherapy for major salivary gland carcinomas: Subanalysis of J-CROS 1402 HN.

A retrospective multicenter study was carried out 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 four 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, seven patients had grade 3 mucositis and seven had grade 3 dermatitis. Regarding late toxicities, one patient had grade 3 dysphagia and one 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.

Multi-institutional retrospective study of mucoepidermoid carcinoma treated with carbon-ion radiotherapy.

This study aimed to evaluate the clinical outcomes of patients with mucoepidermoid carcinomas in the head and neck treated with carbon-ion radiotherapy. Data from 26 patients who underwent carbon-ion radiotherapy in four facilities were analyzed in this multi-institutional retrospective study: the Japan Carbon-ion Radiation Oncology Study Group. The median follow-up time was 34 months. One patient experienced local recurrence, and the 3-year local control rate was 95%. One patient developed lymph node recurrence and five developed distant metastases. The 3-year progression-free survival rate was 73%. Five patients died, two of mucoepidermoid carcinoma and three of intercurrent disease. The 3-year overall survival rate was 89%. Acute mucositis and dermatitis of grade 3 or higher were experienced by 19% and 8% of patients, respectively; these improved with conservative therapy. Late mucositis and osteonecrosis of jaw were observed in 12% and 23% of patients, respectively. The 3-year cumulative rate of any late adverse event of grade 3 or higher was 14%. None of the patients died of the acute or late adverse events. Carbon-ion radiotherapy was efficacious and safe for treating mucoepidermoid carcinoma in this multi-institutional retrospective study (registration no. UMIN000024473). We are currently undertaking a prospective multicenter study.

Particle radiotherapy for prostate cancer.

Recent advances in external beam radiotherapy have allowed us to deliver higher doses to the tumors while decreasing doses to the surrounding tissues. Dose escalation using high-precision radiotherapy has improved the treatment outcomes of prostate cancer. Intensity-modulated radiation therapy has been widely used throughout the world as the most advanced form of photon radiotherapy. In contrast, particle radiotherapy has also been under development, and has been used as an effective and non-invasive radiation modality for prostate and other cancers. Among the particles used in such treatments, protons and carbon ions have the physical advantage that the dose can be focused on the tumor with only minimal exposure of the surrounding normal tissues. Furthermore, carbon ions also have radiobiological advantages that include higher killing effects on intrinsic radio-resistant tumors, hypoxic tumor cells and tumor cells in the G0 or S phase. However, the degree of clinical benefit derived from these theoretical advantages in the treatment of prostate cancer has not been adequately determined. The present article reviews the available literature on the use of particle radiotherapy for prostate cancer as well as the literature on the physical and radiobiological properties of this treatment, and discusses the role and the relative merits of particle radiotherapy compared with current photon-based radiotherapy, with a focus on proton beam therapy and carbon ion radiotherapy.

Five-Year Survival Outcomes After Carbon-Ion Radiotherapy for Operable Stage I NSCLC: A Japanese National Registry Study (J-CROS-LUNG).

INTRODUCTION: The standard therapy for stage I NSCLC is surgery, but some operable patients refuse this option and instead undergo radiotherapy. Carbon-ion radiotherapy (CIRT) is a type of radiotherapy. The Japanese prospective nationwide registry study on CIRT began in 2016. Here, we analyzed real-world clinical outcomes of CIRT for operable patients with stage I NSCLC. METHODS: All patients with operable stage I NSCLC treated with CIRT in Japan between 2016 and 2018 were enrolled. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. CIRT was delivered to the primary tumor, not to lymph nodes. RESULTS: The median follow-up period was 56 months. Among 136 patients, 117 (86%) had clinical stage IA NSCLC and 19 (14%) had clinical stage IB NSCLC. There were 50 patients (37%) diagnosed clinically without having been diagnosed histologically. Most tumors (97%) were located in the periphery. The 5-year overall survival, cause-specific survival, progression-free survival, and local control rate were 81.8% (95% confidence interval [CI]: 75.1-89.2), 91.2% (95% CI: 86.0-96.8), 65.9% (95% CI: 58.2-74.6), and 95.8% (95% CI: 92.3-99.5), respectively. Multivariate analysis identified age as a significant factor for overall survival (p = 0.018), whereas age and consolidation/tumor ratio (p = 0.010 and p = 0.004) were significant factors for progression-free survival. There was no grade 4 or higher toxicity. Grade 3 radiation pneumonitis occurred in one patient. CONCLUSIONS: This study reports the long-term outcomes of CIRT for operable NSCLC in the real world. CIRT for operable patients has been found to have favorable outcomes, with tolerable toxicity.

Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry.

BACKGROUND AND PURPOSE: To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. MATERIALS AND METHODS: This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. RESULTS: A total of 274 patiets were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7-49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %-85.5 %) and OS was 92.5 % (95 % CI: 89.3 %-95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. CONCLUSIONS: Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery.

Clinical results of carbon ion radiotherapy for inoperable stage I non-small cell lung cancer: A Japanese national registry study (J-CROS-LUNG).

BACKGROUND AND PURPOSE: Radiotherapy is a standard treatment for inoperable stage I non-small cell lung cancer (NSCLC), and carbon-ion radiation therapy (CIRT) may be used for such treatment. Although CIRT for stage I NSCLC has demonstrated favorable outcomes in previous reports, the reports covered only single-institution studies. We conducted a prospective nationwide registry study including all CIRT institutions in Japan. MATERIALS AND METHODS: Ninety-five patients with inoperable stage I NSCLC were treated by CIRT between May 2016 and June 2018. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. RESULTS: The median patient age was 77 years. Comorbidity rates for chronic obstructive pulmonary disease and interstitial pneumonia were 43% and 26%, respectively. The most common schedule for CIRT was 60 Gy (relative biological effectiveness (RBE)) in four fractions, and the second most common was 50 Gy (RBE) in one fraction. The 3-year overall survival, cause-specific survival, and local control rates were 59.3%, 77.1%, and 87.3%, respectively. Female sex and ECOG performance status of 0-1 were favorable prognostic factors for overall survival in a multivariate analysis. No grade 4 or higher adverse event was observed. The 3-year cumulative incidence of grade 2 or higher radiation pneumonitis was 3.2%. The risk factors for grade 2 or higher radiation pneumonitis were a force expiratory volume in 1 second (FEV1) of <0.9 L and a total does of ≥ 67 Gy(RBE). CONCLUSION: This study provides real-world treatment outcomes of CIRT for inoperable. stage I NSCLC in Japan.

Clinical results of carbon-ion radiotherapy for stage I non-small cell lung cancer with concomitant interstitial lung disease: a Japanese national registry study (J-CROS-LUNG).

Anti-cancer treatments for lung cancer patients with interstitial lung disease (ILD) are challenging. The treatment options for ILD are often limited because of concerns that treatments can cause acute exacerbation (AE) of ILD. This study aimed to analyze the outcomes of carbon-ion radiotherapy (CIRT) for stage I non-small cell lung cancer (NSCLC) with ILD, using a multi-institutional registry. Patients with ILD who received CIRT for stage I NSCLC in CIRT institutions in Japan were enrolled. The indication for CIRT was determined by an institutional multidisciplinary tumor board, and CIRT was performed in accordance with institutional protocols. Thirty patients were eligible. The median follow-up duration was 30.3 months (range, 2.5-58 months), and the total dose ranged from 50 Gy (relative biological effectiveness [RBE]) to 69.6 Gy (RBE), and five different patterns of fractionation were used. The beam delivery method was passive beam in 19 patients and scanning beam in 11 patients. The 3-year overall survival (OS), cause-specific survival, disease-free survival (DFS) and local control (LC) rates were 48.2%, 62.2%, 41.2% and 88.1%, respectively. Grade > 2 radiation pneumonitis occurred in one patient (3.3%). In conclusion, CIRT is a safe treatment modality for stage I NSCLC with concomitant ILD. CIRT is a safe and feasible treatment option for early lung cancer in ILD patients.

Multicenter study of re-irradiation using carbon-ions for head and neck malignancies after photon radiotherapy.

PURPOSE: The goal of this multicenter retrospective study of patients with head and neck malignancies was to evaluate the efficacy and safety of carbon-ion (C-ion) radiotherapy (RT) after photon RT. METHODS: We enrolled 56 patients with head and neck malignancies who underwent re-irradiation (re-RT) using C-ions between November 2003 and March 2019, treated previously with photon RT. The tumors at re-RT were located in the sinonasal cavities (n = 20, 35.7%), skull base (n = 12, 21.4%), and orbit (n = 7, 12.5%). The tumors at the initial RT were located in the sinonasal cavities (n = 13, 23.2%), skull base (n = 9, 16.1%), and orbit (n = 9, 16.1%). The median period between the initial RT and re-RT was 41 (4-568) months. The most common histology of re-RT was squamous cell carcinoma (n = 11, 19.6%). The most commonly used protocol was 57.6 Gy (relative biological effectiveness) in 16 fractions (n = 23, 41.1%). Surgery preceded re-RT in three patients (5.4%). One patient with malignant melanoma received concurrent chemotherapy. RESULTS: The 2-year local control, progression-free survival, and overall survival rates were 66.5%, 36.9%, and 67.9%, respectively. The median follow-up time was 28 months. Two patients (3.6%) developed grade ≥ 3 acute toxicities, and 14 (25.0%) developed grade ≥ 3 late toxicities. A single patient had confirmed grade 5 dermatitis with infection. CONCLUSION: Re-RT using C-ions for head and neck malignancies after photon RT is an effective treatment with tolerable toxicity.

Radiation-Induced Olfactory Neuroblastoma Following Treatment for NK/T-cell Lymphoma, Nasal Type.

Radiation-induced olfactory neuroblastoma (ONB) is an uncommon neoplasm that is generally associated with a poor prognosis. We experienced an unusual case of ONB in a patient who had received previous radiation therapy for extranodal NK/T-cell lymphoma 15 years previously. To our knowledge, this is the first report of a patient with radiation-induced ONB obtaining a complete response (CR) with radical re-irradiation alone. The purpose of this report is to discuss therapeutic strategies for radiation-induced ONB. We report an unusual case of ONB suspected to be a radiation-induced neoplasm in a 33-year-old female who had received 30 Gy of irradiation for extranodal NK/T-cell lymphoma, nasal type (NTCL) 15 years earlier. In this case, the patient presented with nasal obstruction and frequent epistaxis. The patient was diagnosed with ONB based on left nasal biopsy findings. The surrounding normal tissues tolerance of nasal ONB radiation had to be limited, because the previously radiated NTCL was located adjacent to critical organs. We performed intensity modulated radiation therapy (IMRT), which could offer precise irradiation (60 Gy in 2 Gy daily fractions) while sparing critical tissues. The present case was treated with radiation therapy alone, whereas previously reported cases were treated with a combination of chemotherapy and radiation therapy. We treated radiation-induced OBN successfully with radical re-irradiation using IMRT alone and the patient has had no recurrence for 3 years.

[Treatment with low-dose cyclophosphamide and radiation therapy for advanced non-small lung cancer in elderly patient].

The patient was a 70-year-old man who had unresectable locally advanced large-cell lung cancer with aorta and mediastimun invasion(T4N2M0). He had left shoulder pain and obstructive pneumonitis caused by lung cancer.We performed 60 Gy/ 35 Fr radiotherapy with concurrent low-dose cyclophosphamide(5mg/body/day). After chemoradiotherapy, the main tumor has been decreasing gradually. Seven years and six months after chemoradiotherapy, we detected the soft tissue mass lesion on his chest CT, but could not find abnormal accumulation on his 18F-FDG-PET. The local control was improved gradually and he had no respiratory symptoms or pain for a long period. There has been no recurrence for 10 years now. We recommend radiation and/or low-dose chemotherapy as useful treatments for the advanced non-small lung cancer in elderly patients.

Multicenter Study of Carbon-ion Radiotherapy for Oropharyngeal Non-squamous Cell Carcinoma.

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

Analysis of radioactive implant migration in patients treated with iodine-125 seeds for permanent prostate brachytherapy with MRI-classified median lobe hyperplasia.

PURPOSE: Prostate cancer with median lobe hyperplasia (MLH) is a relative contraindication for permanent prostate brachytherapy (PPB) because of an increased risk of post-implant dysuria and technical difficulties associated with achieving stability while implanting within the intravesical tissue. We examined treatment outcome, seed migration, and urination disorders after treatment in MLH patients in order to determine to what degree MLH implants could be stabilized. MATERIAL AND METHODS: Between March 2007 and December 2016, 32 patients had MLH identified radiologically on magnetic resonance imaging, and 193 patients did not have MLH (non-MLH). All patients were treated with loose seeds. In this study, seed migration was defined as a seed distant from the target (≥ 1.5 cm) and/or with no dosimetric contribution to the target. The MLH patients were divided into 2 MLH groups of mild (< 10 mm) and severe (≥ 10 mm) MLH by measuring the distance between the posterior transitional zone and the prostatic tissue protruding into the bladder. We retrospectively analyzed seed migration, dose-volume histograms (DVH), and genitourinary toxicity. RESULTS: MLH was classified as mild in 24 patients and severe in 8. Seed migration occurred in 61 (31.6%) of 193 non-MLH patients and 10 (31.5%) of 32 MLH patients. Implant seed migration and low-dose level of median lobe tended to be high in severe MLH cases. International Prostate Symptom Score (IPSS) peaked one month after implantation, but then resolved slowly and returned to around the pre-treatment level after one year. There were no severe complications. CONCLUSIONS: MLH does not appear to be a strong contraindication for low-dose-rate brachytherapy. However, we found that the seed migration and degree of cold spots tended to be higher in severe MLH cases than in others; therefore, close attention when treating severe MLH cases must be paid.

Multicenter study of carbon-ion radiation therapy for nonsquamous cell carcinomas of the oral cavity.

BACKGROUND: 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. METHODS: Retrospective analysis of the clinicopathological features and outcomes of 76 patients with oral nonsquamous cell carcinomas with N0-1 M0 status and were treated with carbon-ion radiation therapy at four institutions in Japan between November 2003 and December 2014 was performed. RESULTS: Salivary gland carcinoma, mucosal melanoma, and three other carcinomas were found in 46, 27, and 3 patients, respectively. T1-3, T4a, and T4b disease was diagnosed in 27, 18, and 31 patients, respectively. Median follow-up period was 31.1 months (range, 3-118 months). Three-year local control, progression-free survival, and overall survival of all patients were 86.8%, 63.1%, and 78.4%, respectively. Multivariate analysis showed T classification (T4) to be a significant independent poor prognostic factor for local control. Acute grade 3 mucositis was observed in 38 patients. Grades 3 and 4 late morbidities were observed in 9 and 4 patients, respectively. No grade 5 late toxicity was observed. CONCLUSIONS: Oral nonsquamous cell carcinomas could be treated effectively, with acceptable toxicity, by carbon-ion radiation therapy.

A retrospective multicenter study of carbon-ion radiotherapy for external auditory canal and middle ear carcinomas.

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.

Variation of clinical target volume definition among Japanese radiation oncologists in external beam radiotherapy for prostate cancer.

BACKGROUND: We investigated the interobserver variation in the prostate target volume and the trend toward the use of diagnostic computed tomography (CT) or magnetic resonance (MR) images for treatment planning. METHODS: Twenty-five radiation oncologists were asked to draw the external contour of the prostate on CT images (0.3 cm spacing) of a patient with localized prostate cancer. They also answered a questionnaire regarding the use of diagnostic CT or MR images for the contouring. RESULTS: Of the 25 physicians, 28% rarely or never referred to the diagnostic CT images. In contrast, the physicians tended to refer to the MR images more frequently. Approximately 50% of the physicians believed in the usefulness of contrast-enhanced images for the delineation of the prostate. As for the variation of the prostate contouring, the median craniocaudal prostate length was 36 mm (range, 21-54 mm), and the median prostate volume was 43.5 cm(3) (range, 23.8-98.3 cm(3)). The interobserver variability was not significant in the duration as a radiation oncologist, the board certification status as radiation oncologists, and the number of treatment plans developed for prostate cancer during the last 1 year. CONCLUSION: A wide variety of the definitions of the prostate was found among Japanese radiation oncologists.

[A 23-year delayed locoregional recurrence of breast carcinoma following mastectomy].

A 77-year-old woman who underwent a right modified radical mastectomy 23 years ago with no further adjuvant treatment presented with a right chest wall mass (3 x 4 x 2 cm) at the scar. She had no symptoms nor metastasis. The laboratory data were normal including tumor marker. The mass was diagnosed as compatible with a local recurrence tumor from the previous breast cancer on the ultrasonography and chest CT. After obtaining her informed consent for the therapy, we performed 60 Gy/30 fr radiotherapy on the recurrent tumor on her right chest wall with concurrent oral chemo-endocrine therapy. The first regimens were tamoxifen 20 mg/day and 5'-DFUR 600 mg/day, followed by toremifene 80 mg/day and 5'-DFUR 600 mg/day, and then the tumor disappeared. But three years later, we found tumor regrowth. We changed the regimen, giving 5'-DFUR 1,200 mg/day and cyclophosphamide 100 mg/day for 2 weeks followed by a 1-week drug-free period, then added 10 Gy/5 fr radiotherapy and hyperthermia twice a week. Final regimens were anastrozole 1 mg/day and capecitabine 900 mg/day. The recurrent tumor decreased and the disease stabilized. After these therapies, she had very good quality of life. We recommend radiation and/or hyperthermia with concurrent oral chemo-endocrine therapy as useful for the delayed recurrence of elderly breast cancer after a modified radical mastectomy.

A single institutional experience of combined carbon-ion radiotherapy and chemotherapy for unresectable locally advanced pancreatic cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for unresectable locally advanced pancreatic cancer (LAPC). METHODS AND MATERIALS: Patients with LAPC treated with definitive C-ion RT between April 2014 and July 2017 were analyzed retrospectively. The prescribed dose was 55.2 Gy (relative biological effectiveness [RBE] weighted absorbed dose) in 12 fractions. Overall survival (OS), local control (LC), progression free survival (PFS), and toxicity were evaluated. RESULTS: Sixty-four patients were enrolled. All patients completed planned course of C-ion RT. The median follow-up time for survivors from the initiation of C-ion RT was 24.4 months (range, 5.1-46.1 months). Median survival time was 25.1 months. Two-year OS, LC, and PFS were 53% (95% confidence interval [CI], 39%-66%), 82% (95% CI, 66%-91%), and 23% (95% CI, 14%-36%), respectively. Four patients experienced acute grade 3 toxicities including 3 gastrointestinal (GI) toxicities. There was no grade 3 or more late toxicity. CONCLUSIONS: The clinical results of C-ion RT for LAPC at our institution were comparable to those of a recent multi-institutional analysis.

Definitive Carbon-Ion Radiation Therapy for Locally Advanced Sinonasal Malignant Tumors: Subgroup Analysis of a Multicenter Study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS).

PURPOSE: To evaluate the safety and efficacy of carbon-ion radiation therapy (C-ion RT) for locally advanced sinonasal malignant tumors in a multicenter retrospective study (J-CROS 1402 HN). METHODS AND MATERIALS: Clinical data were collected for patients who had sinonasal malignant tumors of stage N0-1M0 and received C-ion RT at 4 institutions in Japan between November 2003 and December 2014. Of the 458 patients, 393 had naïve tumors and 65 had recurrent tumors. The tumors were located in the nasal cavity (n = 263), maxillary sinus (n = 109), ethmoid sinus (n = 71), and other locations (n = 15). The histologic types were mucosal melanoma (n = 221, 48%), adenoid cystic carcinoma (n = 122, 27%), squamous cell carcinoma (n = 31, 7%), olfactory neuroblastoma (n = 30, 7%), adenocarcinoma (n = 21, 5%), and other types (n = 33, 7%). Of the 458 patients, 300 (66%) had T4 tumors. All patients received definitive C-ion RT. RESULTS: The median follow-up period was 25.2 months for all patients (range, 1.4-132.3 months). The 2-year overall survival and local control rates were 79.6% and 84.1%, respectively. As analyzed according to histology, the 2-year overall survival rate was 68.0% for mucosal melanoma, 96.8% for adenoid cystic carcinoma, 70.0% for squamous cell carcinoma, 96.7% for olfactory neuroblastoma, and 89.7% for adenocarcinoma. Regarding late toxicities, 17% of patients developed grade 3 and 4 toxicities, of which visual impairment was the most common. CONCLUSION: The results of our multicenter study have demonstrated that C-ion RT can provide excellent clinical outcomes with acceptable late toxicities in patients who have locally advanced sinonasal malignant tumors.

A multi-institutional retrospective study of carbon-ion radiotherapy for non-squamous cell malignant tumors of the nasopharynx: Subanalysis of Japan Carbon-Ion Radiation Oncology Study Group study 1402 HN.

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.

A Retrospective Multicenter Study of Carbon Ion Radiotherapy for Locally Advanced Olfactory Neuroblastomas.

The purpose was to evaluate efficacy and safety of carbon ion radiotherapy (C-ion RT) in patients with locally advanced olfactory neuroblastomas (ONBs). This study was a sub-analysis of the Japan Carbon-Ion Radiation Oncology Study Group Study (1402 HN, UMIN000024473). Clinical data of T4 ONBs treated with C-ion RT at four Institutions between November 2003 and December 2014 were retrospectively reviewed. Twenty-one patients underwent C-ion RT. Seven patients had T4a and 14 had T4b tumours without cervical node metastases. The median follow-up period was 39 (range=5-111) months. The 3-year overall survival and local control rates were 88.4% and 83.0%, respectively. Grade 4 late toxicity was observed in three patients, including ipsilateral optic nerve disorder (n=2) and ipsilateral retinopathy (n=1). C-Ion RT is effective and can be a curative modality for T4 ONBs. Prospective multicenter studies are warranted to confirm these findings.