Recent developments in the field of radiotherapy for the management of lung cancer.

Lung cancer has a poor prognosis, and further improvements in outcomes are needed. Radiotherapy plays an important role in the treatment of unresectable lung cancer, and there have been recent developments in the field of radiotherapy for the management of lung cancer. However, to date, there have been few reviews on the improvement in treatment outcomes associated with high precision radiotherapy for lung cancer. Thus, this review aimed to summarize the recent developments in radiotherapy techniques and indicate the future directions in the use of radiotherapy for lung cancer. Stereotactic body radiotherapy (SBRT) for unresectable stage I lung cancer has been reported to improve local control rates without severe adverse events, such as radiation pneumonitis. For locally advanced lung cancer, a combination of chemoradiotherapy and adjuvant immune checkpoint inhibitors dramatically improves treatment outcomes, and intensity-modulated radiotherapy (IMRT) enables safer radiation therapy with less frequent pneumonitis. Particle beam therapy, such as carbon-ion radiotherapy and proton beam therapy, has been administered as advanced medical care for patients with lung cancer. Since 2024, it has been covered under insurance for early stage lung cancer with tumors ≤ 5 cm in size in Japan. In addition to chemotherapy, local ablative radiotherapy improves treatment outcomes in patients with oligometastatic stage IV lung cancer. A particular problem with radiotherapy for lung cancer is that the target location changes with respiratory motion, and various physical methods have been used to control respiratory motion. Recently, coronavirus disease has had a major impact on lung cancer treatment, and cancer treatment during situations, such as the coronavirus pandemic, must be performed carefully. To improve treatment outcomes for lung cancer, it is necessary to fully utilize evolving radiotherapy modalities, and the role of radiotherapy in lung cancer treatment is expected to increase.

Criteria for Treatment of Intranasal Supernumerary Teeth: A Comprehensive Literature Analysis.

Objectives: Among oral surgical conditions, supernumerary teeth of the dental arch is quite common. However, supernumerary teeth in the nasal cavity is a rarity and their diagnosis and treatment have not yet been systematized. We therefore examined the literature on intranasal supernumerary teeth to establish systematic methods for their diagnosis and treatment. Methods: Using the PubMed database, we searched for literature on intranasal supernumerary teeth, published from 1990 to 2019. We combined 131 cases identified in the literature with 1 case that we experienced and summarized the characteristics of 132 cases. We recorded data on sex, age, reason for consultation (chief complaint), reporting department, impact classification, surgical approach, and anesthesia. Results: Males outnumbered females in all decades evaluated. The median age of patients was 10 years. The characteristics of these cases resembled those of maxillary anterior supernumerary teeth. The most common reason for consultation in earlier years was nasal symptoms; however, over time, an increasing number of patients sought consultation due to indications in diagnostic imaging. The most common reporting department in all decades was Otolaryngology. However, reports from Departments of Oral Surgery became increasingly common over time. General anesthesia was applicable for all impaction positions and surgical methods used. Local anesthesia was performed only with the nasal method. Of the 132 patients, 4 experienced no effect from local anesthesia, which was then changed to general anesthesia. Intranasal supernumerary teeth were found to possess the same characteristics as impacted maxillary central supernumerary teeth. Conclusions: The increased use of computed tomography has enabled early detection in asymptomatic cases. Classifying intranasal supernumerary teeth by their vertical and horizontal impaction positions provides an accurate grasp of supernumerary tooth impact classification and the selection of suitable methods of surgery and anesthesia, thus enabling systematic diagnosis and treatment of intranasal supernumerary teeth.

Undifferentiated Pleomorphic Sarcoma Invading the Internal Jugular Vein.

A 60-year-old woman received carbon ion radiotherapy (C-ion RT) (70.4 Gy [relative biological effectiveness]/16 fr) for undifferentiated pleomorphic sarcoma (UPS) (T4bN0M0) in the left pterygopalatine fossa. After 26 months, left parotid resection and left neck dissection were performed for lymph node metastasis in the left parotid gland (no irradiation field). Pathological findings revealed a lymph node with UPS metastasis in the left parotid gland. However, no other metastases in the left cervical lymph node or vascular invasion were observed. Four months after surgery, magnetic resonance imaging revealed an invasion of the left internal jugular vein. Pathological examination of the vascular lesion was not possible because the patient did not consent to surgery. Undifferentiated pleomorphic sarcoma most commonly metastasizes to the lung, and there is currently no known report of vascular invasion. In this case, vascular invasion possibly developed due to changes in the perivascular tissues after the left neck dissection, which may have facilitated tumor invasion into the vascular wall. Based on the images and the clinical course, a rare condition for vascular invasion from UPS recurrence was considered.

Efficacy of immune checkpoint inhibitor treatment for head and neck mucosal melanoma recurrence in patients treated with carbon-ion radiotherapy.

BACKGROUND: Carbon-ion radiotherapy (C-ion RT) is effective for head and neck mucosal melanoma (HN-MM), including radioresistant mucosal melanoma. Melanoma also responds effectively to immune checkpoint inhibitors (ICIs). Data on the efficacy and safety of ICIs for HN-MM are insufficient. AIMS: To analyze the efficacy and safety of ICI salvage therapy in patients with HN-MM recurrence after C-ion RT. METHODS AND RESULTS: This retrospective study analyzed the medical records of 52 patients with HN-MM treated with C-ion RT between 2012 and 2020. A dose of 57.6 or 64.0 Gy (relative biological effectiveness) was provided in 16 fractions. The primary endpoint was 3-year overall survival (OS) rate. The median follow-up time was 26.8 months for all patients. A total of 29 patients had local recurrence or distant metastasis, and 16 patients who received ICI therapy. The 3-year OS rate in the ICI group (n = 16) and best supportive care group (n = 13) were 53.8% and 0.0%, respectively (p = 0.837); the difference was not statistically significant. There were no deaths after 1 year among patients who underwent ICI therapy. No adverse events associated with C-ion RT were related to or exacerbated by ICI. CONCLUSION: ICI salvage therapy is effective and safe for patients with HN-MM recurrence after C-ion RT.

Dose-volume constraints for head-and-neck cancer in carbon ion radiotherapy: A literature review.

BACKGROUND: Carbon ion radiotherapy (CIRT) has been applied in cancer treatment for over 25 years. However, guidelines for dose-volume constraints have not been established yet. The aim of this review is to summarize the dose-volume constraints in CIRT for head-and-neck (HN) cancer that were determined through previous clinical studies based on the Japanese models for relative biological effectiveness (RBE). METHODS: A literature review was conducted to identify all constraints determined for HN cancer CIRT that are based on the Japanese RBE models. RESULTS: Dose-volume constraints are reported for 17 organs at risk (OARs), including the brainstem, ocular structures, masticatory muscles, and skin. Various treatment planning strategies are also presented for reducing the dose delivered to OARs. CONCLUSIONS: The reported constraints will provide assistance during treatment planning to ensure that radiation to OARs is minimized, and thus adverse effects are reduced. Although the constraints are given based on the Japanese RBE models, applying the necessary conversion factors will potentially enable their application by institutions worldwide that use the local effect model for RBE.

Pilot study of aerosols visualized and evaluated in a radiotherapy room.

Health care institutions provide prevention strategies for coronavirus disease 2019 and non-infectious disease care. We investigated the characteristics of patient contamination in a radiotherapy room by examining the trajectory and number of airborne particles in the air when talking and coughing occurred and clarified the actual state of contamination in this closed space. Aerosols were visualized and evaluated in the vertical height and head-to-tail width directions when the participant was lying on the radiotherapy tabletop. Aerosol reach was significantly greater for loud voice and coughing both at vertical height and the head-to-tail width direction. The size and number of particles around the radiotherapy tabletop were also visualized and evaluated in the radiotherapy room. The radiotherapy staff who were in the presence of the participant sometimes had many particles adhering to their facial area; particle adhesion to the staff was dominated by small size particles. Particle adherence to the irradiation device surface near the ceiling had particles larger than 1 mm. Tabletop particles tended to have a wider size range, including bigger sizes and a larger count compared to the surrounding floor. The 0.7-m radius distance from the participant's mouth tended to be highly contaminated, and the smaller the particle size, the farther it reached. The capacity to estimate areas prone to contamination can be used to predict infection of other patients and medical staff in a radiotherapy room.

The Efficacy of Radiotherapy without Surgery for External Auditory Canal Squamous Cell Carcinoma.

External auditory canal (EAC) cancer is a rare disease for which there are no adequate evidence-based treatment strategies. Radiotherapy is often used as the initial treatment to preserve the organ. This study aimed to elucidate the efficacy of radiotherapy for EAC squamous cell carcinoma (SCC). Patients with T1 disease were treated with radiotherapy alone. Patients with T2-4 disease were treated with chemoradiotherapy. The median follow-up period was 30.4 months. The 3-year local control (LC) rate for all patients was 51%, the disease-free survival (DFS) rate was 44%, and the overall survival (OS) rate was 73%. For T1-3 disease, the 3-year LC rate was 74%, DFS was 62%, and OS was 89%. However, for T4 disease, the 3-year LC rate was 17%, DFS was 17%, and OS was 50%. In a univariate analysis, only the T-category was a significant factor for LC and DFS (p = 0.006 and 0.02, respectively). All local recurrences were within the high-dose irradiated area. The results of this study suggest chemoradiotherapy can be an alternative to a combination of surgery and postoperative radiation for T1-3 SCC of the EAC. However, the efficacy of chemoradiotherapy in T4 cases was inadequate.

Dosimetric analysis of intraocular hemorrhage in nonsquamous head and neck cancers treated with carbon-ion radiotherapy.

BACKGROUND AND PURPOSE: Carbon-ion radiotherapy is an attractive treatment option for unresectable/inoperable, nonsquamous cancers of the head and neck. Intraocular hemorrhage associated with carbon-ion radiotherapy for head and neck cancer is largely an unresearched area; hence, we investigated its incidence and predictive factors. MATERIAL AND METHODS: We evaluated 79 patients (i.e., 158 eyes) with nonsquamous cancers of the head and neck treated by carbon-ion radiotherapy with a follow-up period of ≥12 months. Dosimetric parameters such as Dmax, Dmean and Vd [volume irradiated with "d" Gy (RBE)] and age, gender, primary site, histology and comorbidities were analyzed as predictors of intraocular hemorrhage. RESULTS: Seven (8.9%) of 79 patients (158 eyes) developed intraocular hemorrhage with a median latent period of 24 months (range, 15-47 months). The 5-year cumulative incidence of intraocular hemorrhage was 6%. Dmax and V10-60 for eyeballs, retina and optic nerves were significantly higher in intraocular hemorrhage group than the rest (p <0.001 for Dmax and V10-60). On univariate analysis, V40 ≥0.83 cm3 and ≥0.66 cm3 (p = 0.001) and Dmax ≥54.75 Gy (RBE) and ≥54.58 Gy (RBE) (p = 0.002) for eyeball and retina, respectively, were predictors of intraocular hemorrhage. Additionally, maxillary primary (p = 0.025) and younger age (age <60 years, p = 0.048) were significant risk factors for intraocular hemorrhage. CONCLUSIONS: Dosimetric parameters such as V40 and Dmax for the eyeball, retina and maxillary sinus primary and younger age were significant predictors of intraocular hemorrhage following carbon-ion radiotherapy.

Carbon-ion Radiotherapy for Inoperable Head and Neck Bone and Soft-tissue Sarcoma: Prospective Observational Study.

BACKGROUND/AIM: Bone and soft-tissue sarcomas of the head and neck have very poor prognoses. This prospective study aimed to investigate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for bone and soft-tissue sarcoma of the head and neck. PATIENTS AND METHODS: The present study was a prospective clinical study that included 10 consecutive patients diagnosed with bone and soft-tissue sarcoma of the head and neck who were treated with C-ion RT between 2012 and 2018 at our institution. C-Ion RT consisted of 70.4 Gy (relative biological effectiveness) in 16 fractions. RESULTS: The 3-year local control, overall survival, and progression-free survival rates for patients overall were 72.9%, 77.8%, and 36%, respectively. CONCLUSION: The present study demonstrated the efficacy of C-ion RT for bone and soft-tissue sarcoma of the head and neck; adverse events were within the expected range.

Relationship between oral mucositis and the oral bacterial count in patients with head and neck cancer undergoing carbon ion radiotherapy: A prospective study.

BACKGROUND AND PURPOSE: Acute adverse events, such as oral mucositis, can affect treatment success in patients undergoing head and neck radiotherapy. In this study, we aimed to identify the relationship between oral mucositis and oral bacterial counts during carbon ion radiotherapy (C-ion RT) in patients with head and neck cancer. MATERIALS AND METHODS: This prospective study included patients with head and neck tumors treated with C-ion RT between 2017 and 2019. C-ion RT consisted of treatment at 57.6, 64.0, or 70.4 Gy (relative biological effectiveness) in 16 fractions. Bacterial counts in the saliva and the back of the tongue were measured using a rapid oral bacteria quantification system. The relationship between the oral bacterial count and oral mucositis was subsequently analyzed. RESULTS: In total, 46 patients were included in the analysis. The bacterial count in the saliva gradually increased from the commencement of C-ion RT and peaked at 16 fractions. Bacterial counts at the back of the tongue were already high at the beginning of C-ion RT; however, they decreased with continued treatment, peaked at 16 fractions, and subsequently decreased again. Patients with bacterial counts exceeding the mean before C-ion RT (high-count group) did not experience more severe mucositis than those with counts below the mean (low-count group). However, patients in the high-count group tended to experience faster-onset mucositis and slower healing than those in the low-count group. CONCLUSION: Bacterial counts may aid in the development of clinical strategies for C-ion RT-induced oral mucositis.

Oral findings during follow-up of nasopharyngeal squamous cell carcinoma treatment: A case report.

A 50-year-old woman with a long history of nasopharyngeal cancer (T2N2M0, squamous cell carcinoma) underwent chemoradiotherapy and surgery. In the past, to prevent tumor recurrence or metastasis, she underwent concurrent chemoradiotherapy or neck dissection. However, during a follow-up 10 years after the surgery, intense F-18 fluorodeoxyglucose uptake was detected in the oral area (SUVmax 6.0). A biopsy of the area with F-18 fluorodeoxyglucose uptake revealed pathological inflammation. Radiography showed the presence of a wisdom tooth, located at the F-18 fluorodeoxyglucose accumulation site, and pericoronitis of this tooth was detected. Our findings indicate the importance of considering the effect of inflammatory conditions, such as periodontal disease, in using F-18 fluorodeoxyglucose positron emission tomography/computed tomography during follow-up after head and neck cancer treatment.

Clinical features and dosimetric evaluation of carbon ion radiation-induced osteoradionecrosis of mandible in head and neck tumors.

BACKGROUND AND PURPOSE: Osteoradionecrosis (ORN) affects the patient's quality of life by making eating and maintaining oral hygiene painful. This study aimed to analyze carbon ion radiotherapy (C-ion RT)-induced ORN of the mandible. MATERIALS AND METHODS: A retrospective study of 199 patients with head and neck tumors treated with C-ion RT was performed from 2010 to 2019. Only 11 patients with tumors located in the oropharynx and floor of the mouth were analyzed. C-ion RT consisted of 57.6 Gy or 64.0 Gy (relative biological effectiveness) in 16 fractions. The mandible was analyzed for magnetic resonance imaging (MRI) changes and bone exposure. The relationship between the radiation dose and ORN of the mandible was analyzed. RESULTS: Five patients (45.5%) had ORN of the mandible. The median follow-up time was 68 months. The median onset times based on MRI changes and bone exposure were 9 and 15 months, respectively. Doses of 30 Gy (relative biological effectiveness) to the mandible and teeth showed the most significant effect, causing ORN at 29.5 ± 6.7 cc and 3.9 ± 1.8 cc, respectively, with cut-off values at 16.5 cc (p = 0.002) and 1.8 cc (p = 0.0059), respectively. CONCLUSION: This is the first study reporting the incidence, onset time, and risk-predictive dosimetry parameters of C-ion RT-induced ORN of the mandible. Our study will be useful for establishing clinical strategies for C-ion RT to the head and neck near the mandible.

Stereotactic body radiotherapy for adenoid cystic carcinoma metastatic to the lung: a case report.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare malignant tumor involving mostly the head and neck region, and frequently the salivary glands. The development of lung metastasis after treatment of the primary tumor is a common occurrence in ACC. Although lung metastases show a slow rate of growth, approximately 10% of patients die from distant metastases. The radioresistance of ACC limits the efficacy of conventional radiotherapy for lung metastases, and the optimal dose remains to be determined. Stereotactic body radiotherapy (SBRT) using CyberKnife can deliver a high dose to the lung tumor, while sparing the surrounding normal lung tissues, leading to favorable local control in non-squamous cell lung cancer and metastatic lung tumors. We report a case of lung metastases from ACC treated successfully with SBRT using CyberKnife. CASE PRESENTATION: A 76-year-old Japanese man with ACC who was treated with carbon ion radiotherapy for a primary oropharynx tumor presented with three metastatic lesions in the lung. The tumor masses were located in the right upper, right lower, and left lower lobes of the lungs. Surgical resection was not indicated because of the presence of multiple tumors. The patient underwent SBRT at 60 Gy in 10 sequential fractions for each tumor. The biologically effective dose based on an alpha/beta ratio of 2 Gy was 240 Gy per tumor. The percentage of the total lung volume irradiated with >20 Gy was 4.9%, 3.2%, and 2.6% for each tumor. The patient developed acute radiation pneumonitis during the initial therapy, which resolved at 6 months after the CyberKnife treatment. At 21 months after the first CyberKnife treatment, three tumors showed no signs of recurrence. No late toxicity was observed. CONCLUSIONS: SBRT using CyberKnife is an effective and feasible approach to the management of multiple lung metastases of ACC.

Elongated Styloid Process With Skeletal Mandibular Protrusion.

ABSTRACT: An elongated styloid process (ESP) causes symptoms such as pharyngeal pain, swallowing pain, and discomfort during mouth opening. The main treatment is surgical resection of the ESP. The authors present a case of ESP with skeletal mandibular protrusion. Because mandibular setback by sagittal splitting ramus osteotomy (SSRO) may lead to deterioration of symptoms of ESP, resection of ESP and bilateral SSRO were performed simultaneously. The patient was a 50-year-old man who visited our department with chief complaints of mandibular protrusion and pain in the left pharynx on mouth opening and swallowing. A lateral cephalogram helped in diagnosis of skeletal mandibular protrusion. In addition, an approximately 42-mm left styloid process elongated inferomedially was observed. Left styloidectomy was first performed via the cervical approach, followed by SSRO. Occlusion, facial appearance, and preoperative symptoms due to the ESP improved after surgery. The cervical appearance was esthetically satisfactory. In a case of ESP with skeletal mandibular protrusion with potential aggravation of symptoms because of mandibular setback of the ESP, resection of the styloid process is necessary together with orthognathic surgery.

Evaluation of Carbon Ion Radiation-Induced Trismus in Head and Neck Tumors Using Dose-Volume Histograms.

Carbon ion radiotherapy (C-ion RT) provides a highly localized deposition of energy that can increase radiation doses to tumors while minimizing irradiation of adjacent normal tissues. For tumors located near the temporomandibular joint, C-ion RT-induced trismus may occur. However, the relationship between the carbon ion dose and the onset of trismus is unclear. In this prospective observational study, we assessed the trismus/carbon ion dose relationship using dose-volume histograms in 35 patients who received C-ion RT in their head and neck regions between 2010 and 2014. Trismus was evaluated in patients according to the Common Terminology Criteria for Adverse Events, version 4.0. All patients were treated with 57.6 or 64.0 Gy (relative biological effectiveness (RBE)) in 16 fractions, and the median follow-up time was 57 months. Grade 2 trismus was observed in six patients. The median onset time was 12 months. At maximum radiation doses, all masticatory muscles and coronoid processes, particularly the masseter muscle, were significantly different (p = 0.003). The contouring of the masseter muscle and coronoid process requires different treatment planning. The maximum radiation doses of the coronoid process can be proposed as a guideline for treatment planning, considering the ease of contouring in C-ion RT.

Skin Dose Reduction by Layer-Stacking Irradiation in Carbon Ion Radiotherapy for Parotid Tumors.

Background: Layer-stacking irradiation (LSI) results in the accumulation of multiple small spread-out Bragg peaks along the beam direction. Although the superiority of LSI to conventional passive irradiation (CPI) regarding normal tissue sparing is theoretically evident, the clinical benefit of LSI has not been demonstrated. Here, we compared LSI with CPI using the same treatment planning-computed tomography images used for carbon ion radiotherapy (CIRT). Methods: Twenty-one parotid tumors were analyzed. The clinical target volume (CTV) 1 and CTV2 encompassed the parotid grand and the tumor, respectively. CTV1 and CTV2 received 36 Gy (RBE: relative biological effectiveness) in nine fractions and 64 Gy (RBE) in 16 fractions, respectively, using either LSI or CPI. CTV coverage was assessed by DX%, which is the dose covering at least X% of the target volume. Skin dose was assessed by SX, which is the skin surface area receiving at least X Gy (RBE). Results: For CTV1 and CTV2, there were no significant differences in D2% between LSI and CPI. D50% and D98% were slightly higher for CPI; however, the absolute difference between the two methods was <3%. S10-S60 (in increments of 10) were significantly lower for LSI than for CPI (P < 0.001 for all parameters). LSI was associated with a significant trend toward dose reduction at the skin area irradiated with a higher dose by CPI (P < 0.001). Conclusions: LSI achieved better skin sparing than CPI without sacrificing target volume coverage in parotid tumor patients.

Relative Biological Effectiveness of Carbon Ions for Head-and-Neck Squamous Cell Carcinomas According to Human Papillomavirus Status.

Carbon-ion radiotherapy (CIRT) has strong antitumor effects and excellent dose conformity. In head-and-neck squamous cell carcinoma (HNSCC), human papillomavirus (HPV) status is a prognostic factor for photon radiotherapy outcomes. However, the effect of HPV status on the sensitivity of HNSCCs to carbon ions remains unclear. Here, we showed that the relative biological effectiveness (RBE) of carbon ions over X-rays was higher in HPV-negative cells than in HSGc-C5 cells, which are used for CIRT dose establishment, whereas the RBE in HPV-positive cells was modest. These data indicate that CIRT is more advantageous in HPV-negative than in HPV-positive HNSCCs.

Carbon-ion radiotherapy combined with chemotherapy for head and neck mucosal melanoma: Prospective observational study.

This study aimed to evaluate the efficacy of carbon-ion radiotherapy in combination with chemotherapy using dacarbazine, nimustine, and vincristine (DAV therapy) in mucosal melanoma. Twenty-one patients with clinically localized mucosal melanoma of the head and neck were enrolled. The primary endpoint was 3-year overall survival (OS). Secondary endpoints included local control, progression-free survival (PFS), and adverse event occurrence. Carbon-ion radiotherapy with a dose of 57.6-64.0 Gy (relative biological effectiveness) in 16 fractions was delivered concurrently with DAV therapy, and 2 cycles of adjuvant DAV therapy were administered every 6 weeks. The median follow-up periods were 15.5 months for all patients, and 31.2 months for 12 surviving patients. All patients had locally advanced T4a or T4b disease in the rhino-sinus area. In 16 patients (76.2%), 3 cycles of planned DAV therapy were completed. The 3-year OS and PFS rates were 49.2% and 37.0% respectively. The 3-year local control rate was 92.3%. Eleven patients (52%) developed distant metastasis, which was the most frequent pattern of the first failure. Commonly presenting acute grade 2-3 toxicities associated with radiotherapy and chemotherapy were mucositis (11 patients [53%]) and leukopenia (9 patients [43%]), which improved with conservative therapy. None of the patients developed grade 3 or greater late toxicities. Carbon-ion radiotherapy in combination with DAV therapy led to excellent local control for advanced mucosal melanoma within acceptable toxicities. The efficacy of additional DAV therapy in improving survival was weaker than expected as distant metastases still occurred frequently. Trial registration no. UMIN000007939.

Dosimetric parameters predictive of nasolacrimal duct obstruction after carbon-ion radiotherapy for head and neck carcinoma.

BACKGROUND AND PURPOSE: Little information is available on the risk factors for nasolacrimal duct obstruction after radiotherapy for head and neck tumors. We investigated the incidence and predictive dosimetric parameters for nasolacrimal duct obstruction following carbon-ion radiotherapy for head and neck tumors. MATERIALS AND METHODS: Twenty-eight patients with head and neck non-squamous cell carcinoma were analyzed in this single-institution prospective study. More than half of the tumors were located in the nasal cavity and maxillary sinus. Carbon-ion radiotherapy consisting of 57.6 or 64.0 Gy(relative biological effectiveness; RBE) in 16 fractions was administered. Nasolacrimal duct obstruction was recorded according to Common Terminology Criteria for Adverse Events version 4.0. Cutoff values were determined using receiver operating characteristic (ROC) curve analysis. VX indicates the volume irradiated with X Gy(RBE). RESULTS: The median follow-up period was 60.3 months. Incidences of Grade 1 and 2 nasolacrimal duct obstructions were 46% (13/28) and 7% (2/28), respectively; no Grade 3 or greater toxicities were recorded. Throughout the dose range, the volumes of the irradiated nasolacrimal ducts were significantly higher in the obstruction-positive patients than in the obstruction-negative patients (p < 0.001 for V10, V20, V30, V40, V50, and V60). Cutoff values determined by the ROC curve analysis classified the obstruction-positive patients with an accuracy of >96% over the entire range of V10-V60. CONCLUSION: The incidence and predictive dosimetric parameters for nasolacrimal duct obstruction after carbon-ion radiotherapy were demonstrated in a prospective cohort. These data should help optimize carbon-ion radiotherapy treatments for patients with head and neck tumors.